Neuroblastoma, the most common solid tumor in the first five years of life, presents most of the time as advanced stage disease in children over the age of one year, with little progress made over the past 20 years in a poor survival. Neuroblastomas often secrete the catecholamine metabolites HVA and VMA which can be found in individuals' urine and quantitatively determined, thus lending themselves to preclinical detection. Sensitive and specific quantitative assays for HVA and VMA from urine collected on filter papers have been adapted for use in Quebec, the only area in North America where an infrastructure for urinary mass screening exists. This study will examine the clinical and biologic aspects of screening infants for the development of neuroblastoma. Urine from over 400,000 infants born in the province of Quebec during a five year period of time will be requested at 3 weeks and 6 months of age for screening. Infants who screen positive will undergo a thorough non-invasive diagnostic evaluation for the presence of neuroblastoma, with detected infants then carefully staged, treated and followed-up in a uniform fashion. All other individuals who are diagnosed with neuroblastoma clinically in Quebec and born during the same period of time will be identified and similarly followed. Total screening and treatment costs will be recorded. Clinical staging and outcome of all individuals diagnosed clinically and preclinically in the province, and age specific, population-based mortality from neuroblastoma will be compared to results in appropriate control groups including those clinically in Quebec prior to the project as well as those born during the same time and diagnosed elsewhere; either treater in an identical fashion (Pediatric Oncology Group patients) or diagnosed in the state of Minnesota or the Greater Delaware Valley and identified through these population-based tumor registries. Specific biology parameters known to be prognostic factors in neuroblastomas detected clinically will be studied in individuals preclinically detected to determine if they are of equal importance. These parameters include: tumor N-myc oncogene amplification and expression, DNA content, cytogenetics, gangliosides, and histology; serum ferritin, neuron-specific enolase, and gangliosides: and urinary catecholamine metabolites. The results obtained in this study will help determine whether screening of North American infants for the detection of neuroblastoma will lead to both a decrease in clinical stage at diagnosis as well as to reduced mortality.
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