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Neuroblastoma Mass Screening in Late Infancy: Insights Into the Biology of Neuroblastic Tumors

Reinhold Kerbl, Christian E. Urban, Inge M. Ambros, Hans J. Dornbusch, Wolfgang Schwinger, Herwig Lackner, R. Ladenstein, V. Strenger, H. Gadner, Peter F. Ambros

From the Department of Pediatrics, University of Graz, Graz; Children’s Cancer Research Institute; St. Anna Children’s Hospital, Vienna, Austria.

Address reprint requests to Reinhold Kerbl, MD, University Children’s Hospital, Auenbruggerplatz 30, A-8036 Graz, Austria; e-mail: reinhold.kerbl{at}uni-graz.at.

Purpose: Neuroblastoma screening in early infancy has detected predominantly "favorable" tumors. We postponed screening to an age between 7 and 12 months to test whether this shift of screening age might influence the detection rate of genetically/clinically unfavorable tumors.

Patients and Methods: In a 10-year period, 313,860 infants were screened by analysis of urine catecholamines. When a neuroblastoma was diagnosed, at least two different areas from every tumor were analyzed for genetic features (MYCN amplification, 1p status, ploidy). Furthermore, neuroblastoma incidence and mortality of the screened group and the cohort of 572,483 children not participating in the screening program were compared.

Results: Forty-six neuroblastomas were detected by mass screening. In 17 tumors (37%) at least one of the biologic features was "unfavorable." In 10 of 17 patients, one or more of these alterations were only focally present (tumor heterogeneity). In the screened cohort, neuroblastoma incidence was significantly higher when compared with unscreened children (18.2 v 11.2/100,000 births), while there was a trend towards lower incidence of stage 4 over 1 year (2.2 v 3.8). Mortality was not significantly different (0.96 v 1.57).

Conclusion: In contrast to other neuroblastoma screening programs, more than one-third of patients were found with unfavorable genetic markers in our study. The high proportion of focal alterations suggests that biologically young neuroblastomas may consist of genetically favorable and unfavorable parts/areas/clones. We conclude that at least one-third of neuroblastomas detected by screening in late infancy are anticipated cases. This, however, does not result in significantly reduced mortality.

This study was supported by the Styrian Government, the Styrian Children’s Cancer Fund, and the Children’s Cancer Research Institute, Vienna, Austria.

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