Abstract

Background
One fourth of infants with disseminated neuroblastoma experience unfavorable outcome. Treatment strategies vary and are based on clinical characteristics at diagnosis which lead to the definition of stage 4 or 4s. To identify the distribution and effect of different prognostic factors, a series of such infants diagnosed in Italy between 1991-1999 was reviewed.
Material and Method
Data were retrospectively retrieved from the Italian Neuroblastoma Registry. One hundred infants, 32 stage 4 and 68 stage 4s, were eligible. Clinical and biological characteristics evaluated at diagnosis for their impact on survival were demographics, primary site, urinary excretion of vanillylmandelic and homovanillic acids, serum neuron specific enolase, LDH, and ferritin together with analysis for MYCN gene, DNA index, and 1p36 chromosome.
Results
Stage 4 prevailed in the second six months of life and stage 4s in the first six months. Events were distributed over two years in stage 4, but occurred very early in stage 4s patients. Survival was respectively 72% and 77.9%. Unfavorable factors were MYCN amplification for both stages, elevated NSE and LDH and normal VMA for stage 4, and di-tetraploid DNA for stage 4s.
Conclusions
The frequency of stage 4s was greater than stage 4. MYCN amplification was the most unfavorable prognostic factor. Survival was similar to previous series, confirming that a part of such infants cannot be cured by current therapies.

Keywords: Prognosis, Vanilmandelic Acid - urine, Survival Rate, Oncogene Proteins - genetics, Phosphopyruvate Hydratase - blood, Nuclear Proteins - genetics, Neuroblastoma - diagnosis, Neoplasm Staging - methods, Neoplasm Metastasis - diagnosis, L-Lactate Dehydrogenase - analysis, Italy, Infant, Newborn, Homovanillic Acid - urine, Genetic Markers - genetics, Ferritins - analysis, Chromosomes, Human, Pair 1 - genetics, Biological Markers - analysis