Evaluation, investigations, and management of late effects of childhood cancer

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).

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Neuropsychological Late Effects

Comprehensive Handbook of Childhood Cancer and Sickle Cell Disease ◽

10.1093/oso/9780195169850.003.0020 ◽

2006 ◽

Author(s):

Raymond K. Mulhern ◽

Robert W. Butler

Keyword(s):

Brain Tumors ◽

Childhood Cancer ◽

Late Effects ◽

Lymphoblastic Leukemia ◽

Future Research ◽

Cognitive Changes ◽

Neuropsychological Status ◽

Neurobiological Substrates ◽

Long Term Survivors

This chapter reviews neuropsychological late effects associated with childhood cancer and its treatment. The study of late effects presupposes that patients are long-term survivors, if not permanently cured, of their disease. Late effects are temporally defined as occurring after the successful completion of medical therapy, usually 2 or more years from the time of diagnosis, and it is generally assumed that late effects are chronic, if not progressive, in their course. This definition serves to separate late effects from those effects of disease and treatment that are acute or subacute and time limited, such as chemotherapy-induced nausea and vomiting or temporary cognitive changes induced by cancer therapy. Research interest in neuropsychological outcomes, as well as neurological and other functional late effects, has shown an increase commensurate with improvements in effective therapy. For example, 30 years ago when few children were cured of acute lymphoblastic leukemia (ALL), questions related to the ultimate academic or vocational performance of long-term survivors were trivial compared to the need for improved therapy. In contrast, today more than 80% of children diagnosed with ALL can be cured, and issues related to their quality of life as long-term survivors have now received increased emphasis. There is at least comparable attention to neuropsychological status in primary brain tumors. We first provide a brief medical background on the two most frequent forms of childhood cancer, ALL and malignant brain tumors, followed by a review of the current neuropsychological literature. The literature review provides an in-depth analysis of the types of cognitive impairments observed and known or suspected risk factors for impairments. When neurobiological substrates are known, particularly from neuroimaging studies, they are discussed. Finally, we conclude the review with sections that discuss current recommendations for a core battery of neuropsychological assessment of survivors and recommendations for future research. Approximately 20,000 children and adolescents under the age of 20 years were diagnosed with cancer in 1999 (Steen & Mirro, 2000). The most commonly diagnosed cancer in this age group is ALL, a malignant disorder of lymphoid cells found in the bone marrow that migrates to virtually every organ system, including the central nervous system (CNS), via the circulatory system. ALL accounts for one fourth of all childhood cancers and 75% of all cases of childhood leukemia (Margolin, Steuber, & Poplack, 2002).

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