Biologic factors determine prognosis in infants with stage IV neuroblastoma: A prospective Children's Cancer Group study

Purpose: A prospective Children's Cancer Group study, CCG-3881, has been co mpleted to determine if a more accurate prediction of prognosis by biologic features can identify subgroups of infants with stage IV neuroblastoma (NB L) who require differing intensities of treatment. 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, S himada histopathologic classification, serum ferritin, and bone marrow immu nocytology (sensitivity, one tumor cell per 10(5) bone marrow cells). patie nts treated on CCG-3881 (n = 116) received four-drug chemotherapy for 9 mon ths (cisplatin, cyclophosphamide, doxorubicin, and etoposide), with surgery and local radiation to residual disease. After January 1991, all subsequen t infants with tumor MYCN amplification (9 = 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, Results: The 3-year event-free survival (EFS) and overall survival (mean +/ - SD) for the 134 infants were 63% +/- 5% and 71% +/- 5%, respectively. pat ients 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 < .00 01). Each of the other biologic features studied had prognostic significanc e in univariate analysis but not after stratifying by MYCN copy number. Conclusion: infants less: than 1 year of age at diagnosis with stage IV NBL have a much improved outcome compared with children greater than or equal to 1 year of age. Nonamplified MYCN tumors identify ct group of infants wit h a 93% +/- 4% EFS, whereas amplified MYCN copy number clearly identifies p atients who are unlikely to survive despite intensive chemotherapy, (C) 200 0 by American Society of Clinical Oncology.