BACKGROUND: Central nervous system (CNS) metastases rarely occur in patients with neuroblastoma, although recent reports suggest an increase in the rate. CNS recurrence may represent a different mechanism of spread than bone and bone marrow metastases and may be associated with unique genetic determinants. Further definition of the radiologic, clinical, and biologic features may provide clues to the predisposing factors and mechanisms of CNS dissemination. METHODS: A retrospective analysis of all children ages 0-21 years with Stage IV neuroblastoma who were diagnosed at the Institut Curie and the Institut Gustave-Roussy between 1985 and 2000 was performed with direct review of medical records and magnetic resonance images, computed tomography scans, and iodine-123 or iodine-131 metaiodobenzylguanidine scintiscans (MIBG scans). When tumor tissue was available, genetic analysis was performed using comparative genomic hybridization (CGH). RESULTS: Of 434 patients with Stage 4 disease, 23 children had the CNS as their site of first recurrence. The estimated risk of CNS recurrence was 8.0% at 3 years, with no significant change in risk over the 15-year period. Eleven patients had isolated CNS recurrences, and the remaining patients developed recurrences concomitantly in other sites. The sites of recurrences were parenchymal (n = 8 patients), parenchymal with meningeal (n = 7 patients), and meningeal alone (n = 8 patients). MIBG scans detected CNS lesions in only 43% of patients. Significant risk factors for CNS recurrence included lumbar puncture at diagnosis, ages 2-3 years, and MYCN gene amplification. Abnormalities that were identified using CGH, in addition to 2p24 amplification in 5/7, included gains of 17q and 18q and losses of 1p, 3p, 10q25-26, and 11q. CONCLUSIONS: The risk of CNS recurrence in patients with neuroblastoma is 8% at 3 years after diagnosis and has not increased in the last 15 years. Because the CNS often is the sole site of recurrence, either it may be a sanctuary site, or the biologic determinants of CNS metastasis may be unique. Elucidation of risk factors and pathogenesis may allow prevention of this fatal event. Cancer 2003;98:155-65. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11448
BACKGROUND: Central nervous system (CNS) metastases rarely occur in patients with neuroblastoma, although recent reports suggest an increase in the rate. CNS recurrence may represent a different mechanism of spread than bone and bone marrow metastases and may be associated with unique genetic determinants. Further definition of the radiologic, clinical, and biologic features may provide clues to the predisposing factors and mechanisms of CNS dissemination. METHODS: A retrospective analysis of all children ages 0-21 years with Stage IV neuroblastoma who were diagnosed at the Institut Curie and the Institut Gustave-Roussy between 1985 and 2000 was performed with direct review of medical records and magnetic resonance images, computed tomography scans, and iodine-123 or iodine-131 metaiodobenzylguanidine scintiscans (MIBG scans). When tumor tissue was available, genetic analysis was performed using comparative genomic hybridization (CGH). RESULTS: Of 434 patients with Stage 4 disease, 23 children had the CNS as their site of first recurrence. The estimated risk of CNS recurrence was 8.0% at 3 years, with no significant change in risk over the 15-year period. Eleven patients had isolated CNS recurrences, and the remaining patients developed recurrences concomitantly in other sites. The sites of recurrences were parenchymal (n = 8 patients), parenchymal with meningeal (n = 7 patients), and meningeal alone (n = 8 patients). MIBG scans detected CNS lesions in only 43% of patients. Significant risk factors for CNS recurrence included lumbar puncture at diagnosis, ages 2-3 years, and MYCN gene amplification. Abnormalities that were identified using CGH, in addition to 2p24 amplification in 5/7, included gains of 17q and 18q and losses of 1p, 3p, 10q25-26, and 11q. CONCLUSIONS: The risk of CNS recurrence in patients with neuroblastoma is 8% at 3 years after diagnosis and has not increased in the last 15 years. Because the CNS often is the sole site of recurrence, either it may be a sanctuary site, or the biologic determinants of CNS metastasis may be unique. Elucidation of risk factors and pathogenesis may allow prevention of this fatal event. Cancer 2003;98:155-65. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11448
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