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Favorable Biology and Outcome of Stage IV-S Neuroblastoma With Supportive Care or Minimal Therapy: A Children’s Cancer Group Study

From the Department of Pediatrics, Marshfield Clinic, Marshfield, WI; Department of Pediatrics, University of California San Francisco, San Francisco; Childrens Hospital of Los Angeles, University of Southern California, and Department of Surgery and Radiation Oncology, University of California Los Angeles, Los Angeles; and Children’s Cancer Group, Arcadia, CA; Childrens Hospital of Philadelphia, Philadelphia, PA; and Vanderbilt Children’s Hospital, Nashville, TN.

Address reprint requests to H. James Nickerson, MD, Children’s Cancer Group, PO Box 60012, Arcadia, CA 91066-6012; email Nickersh{at}mfldclin.edu

PURPOSE: Stage IV-S neuroblastoma is a metastatic disease associated with spontaneous regression and good survival, but 10% to 20% of infants die from early complications. The purpose of this study was to evaluate outcome and prognostic factors in infants with stage IV-S neuroblastoma treated prospectively with supportive care only or, in symptomatic patients, with low-dose cytotoxic therapy.

PATIENTS AND METHODS: Eighty eligible infants were studied for response and survival with supportive care or, for symptomatic patients, cyclophosphamide 5 mg/kg/d for 5 days with or without hepatic radiation of 4.5 Gy over 3 days. Staging was reviewed centrally, and MYCN gene copy number, Shimada histopathologic classification, serum ferritin levels, and bone marrow immunocytology were determined.

RESULTS: Stage IV-S and International Neuroblastoma Staging System stage 4S were 98% concordant. MYCN was not amplified in any of the tumors tested (n = 58), and Shimada histopathologic classification was favorable in 96% (n = 68/71). The 5-year event-free survival (EFS) rate for all infants was 86% and the survival rate was 92%. Supportive care was the only treatment provided for 44 (55%) of 80 infants, and their 5-year survival rate was 100%, compared with 81% survival for those requiring cytotoxic therapy for symptoms (P = .005). Five of six deaths were in infants younger than 2 months of age at diagnosis and were due to complications of extensive abdominal involvement with respiratory compromise or disseminated intravascular coagulation. Although age 3 months at diagnosis was significant for EFS (P = .043), it was less significant for survival (P = .077). The only other significant factor predictive for improved survival was favorable Shimada histopathologic classification. Sites of metastatic involvement (liver, skin, or bone marrow) and surgical resection of the primary tumor were not significant for survival.

CONCLUSION: This study confirms the favorable biologic features and excellent survival of infants with stage IV-S neuroblastoma with minimal therapy. Infants younger than 2 months old at diagnosis with rapidly progressive abdominal disease may benefit from earlier and more intensive treatment.

Contributing Children’s Cancer Group investigators, institutions, and grant numbers are given in the Appendix. Supported by grant no. CA13539 (to Children’s Cancer Group), grant nos. CA22794, CA02649, and CA60104 (to R.C.S.), and grant no. CA 39771 (to G.M.B.) from the Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

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