Biologic Factors Determine Prognosis in Infants With Stage IV Neuroblastoma: A Prospective Children’s Cancer Group Study

  • Mary Lou Schmidt
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • John N. Lukens
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Robert C. Seeger
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Garrett M. Brodeur
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Hiroyuki Shimada
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Robert B. Gerbing
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Daniel O. Stram
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Carlos Perez
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Gerald M. Haase
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...
  • Katherine K. Matthay
    From the Department of PediatricsUniversity of Illinois at Chicago College of Medicine, Chicago, IL; Department of Pediatrics, University of California School of Medicine, San Francisco; Departments of Pediatrics, Pathology, and Preventive Medicine, University of Southern California School of Medicine and Children’s Hospital; University of California Los Angeles School of Medicine, Los Angeles; The Children’s Cancer Group, Arcadia, CA; Department of Pediatrics, University of Pennsylvania School of...

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<jats:p> PURPOSE: A prospective Children’s Cancer Group study, CCG-3881, has been completed to determine if a more accurate prediction of prognosis by biologic features can identify subgroups of infants with stage IV neuroblastoma (NBL) who require differing intensities of treatment. </jats:p><jats:p> PATIENTS AND METHODS: One hundred thirty-four infants were registered from June 1989 to August 1995, with a median follow-up of 47.1 months (range, 0 to 88 months). The biologic factors examined were tumor MYCN copy number, Shimada histopathologic classification, serum ferritin, and bone marrow immunocytology (sensitivity, one tumor cell per 10<jats:sup>5</jats:sup> bone marrow cells). Patients treated on CCG-3881 (n = 116) received four-drug chemotherapy for 9 months (cisplatin, cyclophosphamide, doxorubicin, and etoposide), with surgery and local radiation to residual disease. After January 1991, all subsequent infants with tumor MYCN amplification (n = 18) were transferred after one cycle of therapy to the high-risk CCG-3891 protocol (open January 1991 to April 1996) for more intensive treatment. </jats:p><jats:p> RESULTS: The 3-year event-free survival (EFS) and overall survival (mean ± SD) for the 134 infants were 63% ± 5% and 71% ± 5%, respectively. Patients whose tumors were without MYCN amplification had a 93% ± 4% 3-year EFS, whereas those with amplified MYCN had a 10% ± 7% 3-year EFS (P < .0001). Each of the other biologic features studied had prognostic significance in univariate analysis but not after stratifying by MYCN copy number. </jats:p><jats:p> CONCLUSION: Infants less than 1 year of age at diagnosis with stage IV NBL have a much improved outcome compared with children ≥ 1 year of age. Nonamplified MYCN tumors identify a group of infants with a 93% ± 4% EFS, whereas amplified MYCN copy number clearly identifies patients who are unlikely to survive despite intensive chemotherapy. </jats:p>

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