Neuroblastomas in Denmark 1943-80. Epidemiological and clinical studies

Two-hundred-and-fifty patients were registered in a population-based study of neuroblastomas in Denmark in the period 1943-80. The major epidemiological findings were an increased incidence with an unchanged mortality rate during the study period. The increase in incidence related solely to children 0-4 years of age and was most pronounced in infants under 1 year of age. Several reasons for the observed epidemiological rates include (i) changes in the composition of the population, (ii) improved diagnostic procedures, (iii) a shift in the diagnostic criteria, and (iv) an increase in environmental carcinogens of importance in the induction of neuroblastoma. Associated with an increased risk were lower socio-economic levels and young or advanced parental age, suggesting the importance of environmental as well as genetic factors for the induction of neuroblastoma. The epidemiological findings of an increased incidence with an unchanged mortality rate, which suggests the inclusion of borderline lesions in recent years, are of major importance in interpreting the results of mass screening for the disease. The clinical findings in 253 patients treated in Denmark from 1943 to 1980 (including 5 patients resident outside Denmark and excluding 2 patients without available hospital records) were analysed. The major finding was a zero-time shift, that is, earlier diagnosis of the disease during the study period, with increasing survival rates from decade to decade mostly due to a better age and stage distribution, a zero-time shift which was also apparent in the changes of the symptomatology. Independent prognostic variables were age, stage, and treatment with chemotherapy for children over 1 year of age with stage II disease, and for infants with stages III-IV disease. Analysis of data from a subset of the 253 children suggested that high proliferative activity detected by flow cytometry may be an important prognostic variable. The study also suggests that the pattern of metastatic spread might have changed as a consequence of prolonged survival obtained by improved treatment modalities, stressing the importance of a high frequency of autopsy among cancer patients. Hypotheses generated by the study included (i) that most neuroblastomas might be congenital, (ii) that the age influence on prognosis might be explained in terms of growth rate, cell cycle transit time, and duration of the disease, and (iii) that some neuroblastomas might be borderline lesions.