Originally published as JCO Early Release 10.1200/JCO.2005.05.183 on August 22 2005

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Favorable Prognosis for Patients 12 to 18 Months of Age With Stage 4 Nonamplified MYCN Neuroblastoma: A Children's Cancer Group Study

From the University of Illinois at Chicago, Chicago, IL; Children's Hospital & Research Center Oakland, Oakland; Children's Hospital of Los Angeles, Los Angeles; Children's Oncology Group, Arcadia; University of California, San Francisco School of Medicine, San Francisco, CA; Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia, PA; and University of Minnesota, Minneapolis, MN

Address reprint requests to Mary Lou Schmidt, MD, University of Illinois at Chicago College of Medicine Department of Pediatrics m/c 856 840 S Wood St, Chicago, IL 60612; e-mail: mls3{at}uic.edu

PURPOSE: The long-term survival of children between age 12 and 24 months with stage 4 neuroblastoma and nonamplified MYCN (MYCN-NA) has not been defined previously.

PATIENTS AND METHODS: Survival for stage 4 MYCN-NA neuroblastoma patients enrolled onto Children's Cancer Group (CCG) protocols 321P2 (1986 to 1991) and 3891 (1991 to 1996) was analyzed. Treatment consisted of intensive alkylator-based induction chemotherapy with or without autologous bone marrow transplantation (ABMT) with or without 13 cis-retinoic acid. Survival was analyzed by age strata less than 12, 12 to 18, 18 to 24, and more than 24 months at diagnosis. Patients younger than 12 months were treated on the moderate-intensity CCG protocol 3881.

RESULTS: Forty-three patients with stage 4 MYCN-NA disease enrolled onto CCG-321P2 (n = 17) or CCG-3891 (n = 26) were between 12 and 24 months of age at diagnosis. After a median follow-up of 94 months (range, 4 to 140 months), the 6-year event-free survival (EFS) for the 12- to 18-month age group was superior to that of the 18- to 24-month age group (74% ± 8% v 31% ± 12%; P = .008). The EFS for children older than 24 months with stage 4 MYCN-NA neuroblastoma was 23% ± 3%, and for children younger than 12 months was 92% ± 3%.

CONCLUSION: Children diagnosed with stage 4 MYCN-NA neuroblastoma in the second year of life form a transitional group between infants and older children in terms of prognosis. Patients between 12 and 18 months of age have significantly better long-term survival than that of older children treated with intensive chemotherapy with or without ABMT. These patients may not benefit from additional intensification of therapy beyond that provided in earlier clinical trials and may even maintain this high survival rate with less intensive therapy.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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