Neurocognitive Outcomes in Childhood Cancer: Effects of Disease and Treatment on Brain Development and Learning

Childhood cancer is a rare disease, accounting for only 1% of all malignancies in humans of all ages. In 2007, approximately 10,400 new cases of cancer were diagnosed in children 14 years of age and younger (American Cancer Society 2007). Significant advances in diagnostic techniques and tailored treatments during the past three decades have increased the 5-year survival rate for all cancers to over 80% (Twombly 2007). For acute lymphoblastic leukemia (ALL), the most common form of childhood cancer, the current survival rate is approaching 90% (Pui and Howard 2008). Better survival has led to increased awareness and focus on the consequences of cancer treatment, called late effects. The Children’s Oncology Group has developed and published guidelines for monitoring childhood cancer survivors for late effects in nearly every organ system (Landier et al. 2004), with a recent growing interest in those affecting cognitive, academic, social, and behavioral function (Nathan et al. 2007), which are the focus of this chapter. It was long assumed that a cancer diagnosis and the severe toxicity associated with treatment was such a traumatic event that significant adverse psychological consequences were inevitable. Recent, large reports from the Childhood Cancer Survivorship Study and reviews of smaller studies suggest that this is not the case for the majority of children and adolescents treated for and surviving cancer (Eiser, Hill, and Vance 2000; Zebrack et al. 2002; Zeltzer et al. 2009). With the exception of children who experience central nervous system (CNS) cancer or cancer treatment (Zebrack et al. 2004), most childhood cancer survivors are not significantly different from the general population on measures of depression (Phipps and Srivastava 1999), selfesteem (Noll et al. 1999), hopefulness (Ritchie 2001), or posttraumatic stress disorder (PTSD). Some children experience symptoms of posttraumatic stress during acute treatment, but these symptoms diminish over time (Phipps et al. 2006). For children with CNS cancer or who receive treatment that affects the CNS, the picture is somewhat different, with poorer emotional and social functioning, neurocognitive function, and overall health-related quality of life (HRQL) reported in this subpopulation (Calaminus et al. 2000; Vannatta et al. 2007).