Experience with International Neuroblastoma Staging System and Pathology Classification

International cooperative groups have developed new classifications of neuroblastoma risk groups to compare treatment results internationally and seek effective means to deal with neuroblastoma, particularly in advanced stages. The International Neuroblastoma Staging System (INSS) was originally proposed in 1988, and revised in 1993 (Brodeur et al, 1993). Since then the INSS has been used worldwide (Castleberry et al, 1994; Kaneko et al, 1998), replacing the previous staging systems of different groups. The International Neuroblastoma Pathology Classification (INPC) that is fundamentally based on Shimada's classification was also proposed in 1999 to provide neuroblastoma study groups with a common language (Shimada et al, 1999). However, the clinical importance of these classifications has never been extensively evaluated; Castleberry et al (1994) applied the INSS only retrospectively for their patients treated between 1981 and 1990. Since the predictability of prognostic factors often depends on the intensity or efficacy of treatment, it is important to examine the value of these risk classifications in a study in which highly effective modern treatments are applied (Kawa et al, 1999; Matthay et al, 1999). Clinical results achieved prior to 1991 by us and by others (Brodeur et al, 1984; Seeger et al, 1985; Sawaguchi et al, 1990) clearly showed that patients with MYCN-amplified tumours have a worse prognosis than those without. It was therefore decided in Japan in 1991 to administer intensive induction chemotherapy with a double dose of cyclophosphamide to high-risk patients with MYCN amplification (Kaneko et al, 1998), and that strategy resulted in improved clinical results (Kawa et al, 1999). In the present study we examined the prognostic value of the INSS, the INPC and biological factors including MYCN amplification, DNA ploidy and 1p deletion in patients with neuroblastoma who underwent treatment between 1995 and 1999.