Neuroblastoma is a cancer with heterogeneous clinical manifestations and behaviors. Localized tumors can usually be cured by surgical resection alone (Kushner et al. 1996b; Perez et al. 2000; Brodeur and Maris 2002). At the other end of the spectrum, aggressive metastatic tumors frequently progress despite intensive chemoradiotherapy (Brodeur and Maris 2002). The overall prognosis of high-risk neu-roblastoma patients remains poor, with an overall survival rate of less than 30% at 5 years (Brodeur and Maris 2002); however, with the use of high-dose chemotherapy regimens, plus new drugs, such as cis-retinoic acid, and new modalities of treatment, such as targeted immunotherapy, a subset of patients with high-risk disease achieve and maintain a complete remission (Kushner et al. 1994; Cheung et al. 1998; Matthay et al. 1999; Cheung et al. 2001). Survivors of high-risk neuroblastoma, therefore, face the long-term consequences of intensive multimodality therapy given, often, at a young age.

Only a limited number of studies have assessed the long-term clinical late effects that are specific to survivors of neuroblastoma. The data are particularly scanty on those who have been treated for high-risk disease (Willi et al. 1992; Olshan et al. 1993; Kaste et al. 1998; Kushner et al. 1998; Hovi et al. 1999; Neve et al. 1999; Barr et al. 2000; Koyle et al. 2001; Holtta et al. 2002; Van Santen et al. 2002; Weiss et al. 2003).

In this chapter we review the major and most frequent late complications observed in low/intermediate-risk and high-risk neuroblastoma survivors. Since the radiation fields and the chemotherapeutic agents adopted in neuroblastoma treatment protocols are commonly used to treat other pediatric cancers, published data on late effects in these cancer survivors are highly relevant for children with neu-roblastoma. Additionally, we discuss the late effects observed in a cohort of 65 neuroblastoma survivors, predominantly survivors treated for high-risk disease, who are followed in the Long-Term Follow-Up Clinic at Memorial Sloan Kettering Cancer Center (MSKCC).

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