Subsequent Malignant Neoplasms

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Second malignancy is an unfortunate consequence of childhood cancer treatment. The cumulative estimated incidence of subsequent malignant neoplasms (SMNs) 20 years after a diagnosis of childhood cancer is 3.2% (Neglia et al. 2001). For neuroblastoma survivors, the relative risk of developing an SMN has been reported as 6.59 when compared with the general population, with a cumulative incidence at 20 years of 1.87% (Neglia et al. 2001). This latter estimate is derived from a historical cohort that includes a large number of survivors treated for low/interme diate-risk disease and may not reflect the true risk for patients who are treated with more intensive contemporary regimens.

The most common secondary malignancies reported after neuroblastoma are myelodysplasia/ leukemia, thyroid neoplasm, soft tissue sarcomas, and osteosarcomas (Shah et al. 1983; Meadows et al. 1985; de Vathaire et al. 1989; Tucker et al. 1991; Kushner et al. 1998; Tabone et al. 1999; Schiavetti et al. 2001; Acharya et al. 2003; Garaventa et al. 2003; Le Deley et al. 2003; Weiss et al. 2003). Treatment-related myelodysplasia/leukemia has been well described. The most common chemotherapeutic agents associated with this complication are topoisomerase-II inhibitors (etoposide, doxorubicin) and alkylating agents. The two classes of drugs are associated with specific and different cytogenetic abnormalities (Kushner et al. 1998; Le Deley et al. 2003). Among neuroblastoma survivors treated at MSKCC, Kushner et al. (1998) found a 3-year cumulative incidence of secondary myelodysplasia/leukemia of 7%; therefore, current intensive treatment for high-risk neu-roblastoma is associated with a significant risk for treatment-related acute myeloid leukemia and warrants that these patients be monitored closely.

Secondary thyroid neoplasms are also common in neuroblastoma survivors due to chest and spinal irradiation at a young age (Tucker et al. 1991; Le Deley et al. 2003).

Recently, two studies reported on the risk of SMN (leukemia and solid tumors) with the administration of 131I-MIBG (Garaventa et al. 2003;Weiss et al. 2003). In one of these studies, the cumulative risk of developing a second cancer was 20% within 15 years of receiving 131I-MIBG (Garaventa et al. 2003).

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