For Stage4S Neuroblastoma

Stage 4S neuroblastoma is a well-defined clinical entity that often resolves with minimal or no cytotoxic therapy, but can be lethal from complications of enlarging liver tumors or from progression to classic stage 4 with bone and extensive bone marrow metastases (Berthold and Hero 2000; de Bernardi et al. 1992; DuBois et al. 1999; Evans et al. 1981; Guglielmi et al. 1996; Hachitanda and Hata 1996; Hero et al. 2000; Martinez et al. 1992; Nickerson et al. 2000; Strother et al. 1995; Schleiermacher et al. 2003; van

Figure 11.2.2

Kaplan-Meier event-free survival (EFS) for infants with stage-4 neuroblastoma according to MYCN amplification status treated on the CCG 3881. (From Schmidt et al.2000)

Noesel et al. 1997). This highly variable natural history has complicated management decisions, as has the risk of major sequelae from cytotoxic therapies in these very young patients. In published reports, approximately 50% or more of infants with stage 4S received cytotoxic therapy.

Clinical features of possible prognostic import include age <2-3 months (unfavorable) and skin nodules (favorable). With stage 4S, MYCN amplification is an independent marker of poor outcome and diploidy is considered an adverse risk factor (Bowman et al. 1997; Hachitanda and Hata 1996; Katzenstein et al. 1998; van Noesel et al. 1997); however, the significance of diploidy in the absence of MYCN amplification has not been systematically studied in this subset of infants, and the same holds for unfavorable histopathology. Biologic markers predictive of uncontrollable hepatic enlargement have not, to date, been found. COG uses the presence of diploidy and unfavorable histopathology to confer intermediate-risk status on stage 4S with the implication of a need for treatment with chemotherapy (up to eight cycles in the current COG study); however, this approach is not universally accepted. For example, the German Society of Pediatric Oncology and Hematology recommends observation alone in the absence of MYCN amplification or clinical deterioration (Berthold and Hero 2000; Hero et al. 2000). For symptomatic he patomegaly, low-dose chemotherapy and/or radiotherapy (e.g., 150 cGy/fraction, times three fractions) have been used with variable success (see the present chapter; Schleiermacher et al. 2003).

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