Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival

Purpose: The goal of this study was to determine the incidence of metastati c sites in neuroblastoma and the extent to which metastatic sites correlate with age, tumor biology, and survival. Patients and Methods: All 648 patients with stage TV and TVS neuroblastoma registered on Children's Cancer Group protocols 3881 and 3891 were analyzed . Metastatic site data were provided by treating institutions and reviewed in patients with central nervous system (CNS), intracranial, lung, or "othe r" metastases. Results: The incidence of metastatic sites at diagnosis was 70.5% in bone m arrow, 55.7% in bone, 30.9% in lymph nodes, 29.6% in liver, 18.2% in intrac ranial and orbital sites, 3.3% in lung, and 0.6% in CNS. Event-free surviva l (EFS) was decreased in patients with bone, bone marrow, CNS, intracranial /orbital, lung, and pleural metastases, and improved in those with liver an d skin metastases. In infants, MYCN amplification and unfavorable Shimada h istopathology correlated with increased frequencies of bone and intracrania l or orbital metastases. In older patients, MYCN amplification correlated w ith increased frequencies of intracranial or orbital, liver, and lung metas tases. Multivariate analysis revealed that metastatic site is not an indepe ndent prognostic factor. Conclusions: Metastatic pattern in neuroblastoma differs with age and corre lates with tumor biological features and EFS. These correlations could refl ect changes in host or tumor biological features with age resulting in diff erences in metastatic capacity or tumor affinity for specific sites.