Metastatic Sites in Stage IV and IVS Neuroblastoma Correlate With Age, Tumor Biology, and Survival

Abstract

Metastatic pattern in neuroblastoma differs with age and correlates with tumor biological features and EFS. These correlations could reflect changes in host or tumor biological features with age resulting in differences in metastatic capacity or tumor affinity for specific sites.

Central nervous system metastases in neuroblastoma

“…Tumor samples from the time of diagnosis were examined in 16 patients and showed a predominance of genetic changes connoting very high-risk disease. MYCN amplification was correlated significantly with CNS recurrence, as in the report of DuBois et al, 1 which differs from the report of Kramer et al, 2 who found that only 4 of 11 children had MYCN-amplified tumors, the usual percentage in a Stage 4 high-risk population. Seven patients had detailed studies of their tumor genetics by CGH and demonstrated, in addition to 2p24 amplification, multiple poor prognostic changes, such as gain of 17q and losses of 1p and 11q.…”

“…Headache, nausea, and emesis were associated with parenchymal disease; whereas patients with meningeal disease presented more often with pain, fever, or motor signs. We found a slightly greater proportion of patients with meningeal involvement (65%) compared with what is reported in the literature (47%), [1][2][3][4][12][13][14][15] and this value might have been even greater if routine spinal MRI studies had been performed. The time to CNS recurrence in the literature ranged from 2 months to 34 months, with median similar to the 14 months reported here.…”

“…4 The crude overall incidence in previous series of patients with CNS metastasis was 50 of 1315 patients (3.8%), slightly lower compared with our study. [1][2][3][4][12][13][14][15] However, because the rate of CNS recurrence is dependent on the length of follow-up, and none of the previous reports provided KaplanMeier estimates of recurrence over time, the crude percentage may underestimate the actual risk, which is reported here as 8% at 3 years. Almost all reported CNS metastases have occurred at the time of recurrence rather than at diagnosis.…”

“…A recent report from the Children's Cancer Group (CCG) of metastatic sites in 567 patients with Stage IV disease who were diagnosed between 1989 and 1996 revealed that only 4 patients (0.7%) at diagnosis and 13 patients (2.2%) at recurrence had CNS involvement. 1 Recent reports have suggested that the incidence of CNS recurrence may be increasing and have confirmed that recurrence of neuroblastoma in the CNS is almost uniformly fatal. [2][3][4] It is possible that different sites of CNS recurrence represent different mechanisms of spread, which eventually will be identified with unique genetic patterns.…”

Proapoptotic compound ARC targets Akt and N-myc in neuroblastoma cells

“…Also, possibly as a consequence of the PI3K/Akt pathway inhibition, N-myc protein levels were also reduced in response to ARC treatment. This is especially significant given the fact that one-third of neuroblastoma tumors shows amplification of N-myc, which has a strong correlation with chemotherapy resistance (Norris et al, 1996;DuBois et al, 1999). Though it is still possible that in addition to antagonizing the prosurvival pathways indicated above, ARC-induced apoptosis may also involve as yet unrecognized events, our data provide at least a partial picture of the mechanism of action of ARC and suggest that it could be an attractive candidate for drug development against neuroblastoma tumors.…”