The prognostic value of biological markers in low-risk neuroblastoma is controversial. In part, this is because few events are observed in this cohort of patients and few studies have been performed in which MYCN copy number, DNA index, and histology have been analyzed in large numbers of patients. According to the current COG Risk-Group Schema, stage-4S disease is classified as low risk if all three of these biologic factors are favorable; however, while several studies have indicated that MYCN amplification and unfavorable histology are associated with poor outcome in infants with stage-4S disease (Hachitanda and Hata 1996; Katzenstein et al. 1998; Shimada et al. 1995), the prognostic impact of diploidy in the absence of MYCN amplification is not clear. Although Bourhis et al. found that diploidy correlated with poor outcome in a small study (Bourhis et al. 1991), DNA content was not found to be predictive of out come in stage-4S infants in other studies (Bowman et al. 1997; Look et al. 1991).
Currently, stage 1 in all age groups is considered low risk regardless of biologic markers and the same holds for infants with stage-2 disease. In older patients, lack of MYCN amplification is the only biologic finding needed for classifying stage 2 as low risk. Large Pediatric Oncology Group (POG) and Children's Cancer Group (CCG) studies have demonstrated that MYCN amplification occurs in less 5% of children with INSS stage-1 and stage-2 disease (Al-varado et al. 2000; Perez et al. 2000). In the series reported by Perez et al. 7 patients had MYCN-amplified tumors (Perez et al. 2000). Two of 4 patients with stage-1 disease remain disease free following surgery alone or treatment with surgery and chemotherapy. Of the 3 patients with stage-2B disease, 2 have died of progressive disease. Similarly, MYCN amplification strongly predicted lower EFS and S rates in the POG study (Alvarado et al. 2000); however, the 5-year estimated S rate for this group of patients was 64±27%. Four of 11 patients with MYCN amplification remain disease free after surgical resection alone, and 4 of the 7 patients with relapsed disease were successfully saved with additional therapy. Additional factors are still needed to distinguish those patients with MYCN amplification who will achieve long-term remission with surgery alone from those who will develop recurrent disease.
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