Long-Term Outcomes Among Survivors of Childhood Central Nervous System Malignancies: Late Mortality, Subsequent Neoplasms, Endocrine and Neurologic Morbidity

Abstract

According to the most recent estimates from the Surveillance, Epidemiology and End Results (SEER), 74% of children younger than 20 years of age diagnosed with a central nervous system (CNS) malignancy will become 5-year survivors (Howlader et al. 2012). Current therapy for children with CNS malignancies often includes both surgical resection and a combination of CNS-directed radiation therapy (RT) and chemotherapy. Among survivors of all primary pediatric cancers, survivors of CNS malignancies are at the highest risk for late mortality (Mertens et al. 2001; Taylor and Potish 1985; Dama et al. 2006). Furthermore, survivors of CNS malignancies are at risk for developing subsequent neoplasms and chronic endocrine and neurologic conditions (Neglia et al. 2001; Broniscer et al. 2004; Cardous-Ubbink et al. 2007; Duffner et al. 1998; Devarahally et al. 2003; Peterson et al. 2006; Jenkinson et al. 2004; Hammal et al. 2005; Oeffinger et al. 2006; Packer et al. 2003; Gurney et al. 2003a). Documenting the incidence of and risk factors for these conditions in the second, third, and fourth decades of survival in this aging population is essential as future efforts to reduce late morbidity and mortality through modification and risk stratification of primary therapy, screening and early detection of late effects, and interventions to reduce risk and impact of late effects are dependent on identifying populations at highest risk for poor outcomes. Thus, while 5-year survival has improved, the patterns of late morbidity and mortality after exposure to multimodal therapy are only now being established as this population ages. Future studies will need to identify whether exposure to modern therapies (including focal RT for embryonal CNS tumors in infants, whole ventricular volume RT for germ cell tumors, targeted therapies, and immunotherapy, among others) increases or decreases the risk of long-term morbidity and late mortality compared with patients treated in previous eras (Armstrong et al. 2009a).