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  • Print publication year: 2007
  • Online publication date: August 2009

7 - Neuropsychological sequelae in children treated for cancer


Cancer is the leading cause of death by disease in children under the age of 15 years (National Cancer Institute Research on Childhood Cancers, Cancer Facts). Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer, comprising approximately 40% of all diagnosed cases (Margolin & Poplack, 1997). Brain tumors are the second most frequent malignancy of childhood and the most common of the solid tumors (Ries et al., 2004). Brain tumors and other central nervous system (CNS) cancers account for approximately 20% of all childhood cancers (Sklar, 2002).

Given their higher prevalence amongst childhood cancers and their associated neuropsychological risk, most research into the neuropsychological sequelae of childhood cancer and its related treatment has involved the study of ALL and brain tumors. Such research has become increasingly important as neuropsychological morbidity has increased with the substantial increase in survival rates that has accompanied advances in detection and treatment over the last several decades. Estimated 10-year survival rates for children diagnosed with CNS tumors from 1995 to 1999 were approximately 70% (Brenner, 2003). Five-year survival rates for children with ALL under age 19 now exceed 70% (Ries et al., 2004).

Treatment interventions and associated neuropsychological outcome

Treatment of childhood cancers involving or at risk of involving the CNS varies considerably and is dependent on such factors as tumor type, grade of malignancy, location of the tumor, extent of CNS involvement, and age of the child.

Anderson, V. A., Godber, T., Smibert, E., Weiskop, S. & Ekert, H. (2000). Cognitive and academic outcome following cranial irradiation and chemotherapy in children: A longitudinal study. British Journal of Cancer, 82, 255–62.
Armstrong, F. D., Blumberg, M. J. & Toledano, S. R. (1999). Neurobehavioral issues in childhood cancer. School Psychology Review, 28, 194–204.
Armstrong, F. D. & Reaman, G. H. (2005). Psychological research in childhood cancer: The Children's Oncology Group perspective. Journal of Pediatric Psychology, 30, 89–97.
Barakat, L. P., Hetzke, J. D., Foley, al. (2003). Evaluation of a social skills training group intervention with children treated for brain tumors: A pilot study. Journal of Pediatric Psychology, 28, 299–307.
Beebe, D. W., Ris, M. D., Armstrong, F. al. (2005). Cognitive and adaptive outcomes in low-grade pediatric cerebellar astrocytomas: Evidence of diminished cognitive and adaptive functioning in national collaborative research studies (CCCG 9891/POG 9130). Journal of Clinical Oncology, 2, 5198–204.
Benner, A. E. & Marlow, L. S. (1991). The effect of a workshop on childhood cancer on students' knowledge, concerns, and desire to interact with a classmate with cancer. Children's Health Care, 20, 101–7.
Brenner, H. (2003). Up-to-date survival curves of children with cancer by period analysis. British Journal of Cancer, 8, 1693–7.
Buizer, A. I., Sonneville, L. M., Heuvel-Eibrink, M. M., Njiokiktjien, C. & Veerman, A. J. (2005). Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. Journal of the International Neuropsychological Society, 11, 554–65.
Buono, L. A., Morris, M. K., Morris, R. al. (1998). Evidence for the syndrome of nonverbal learning disabilities in children with brain tumors. Child Neuropsychology, 4, 144–57.
Butler, R. W. (1998). Attentional processes and their remediation in childhood cancer. Medical and Pediatric Oncology, Suppl 1, 75–8.
Butler, R. W. & Copeland, D. R. (2002). Attentional processes and their remediation in children treated for cancer: A literature review and the development of a therapeutic approach. Journal of the International Neuropsychological Society, 8, 115–24.
Butler, R. W. & Mulhern, R. K. (2005). Neurocognitive interventions for children and adolescents surviving cancer. Journal of Pediatric Psychology, 30, 65–78.
Carlson-Green, B., Morris, R. D. & Krawiecki, N. (1995). Family and illness predictors of outcome in pediatric brain tumors. Journal of Pediatric Psychology, 20, 769–84.
Chambless, D. L. & Ollendick, T. H. (2001). Empirically supported psychological interventions: Controversies and evidence. Annual Review of Psychology, 52, 685–716.
Children's Oncology Group. (2004). Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. Retrieved March 18, 2004 from
Fouladi, M., Chintagumpala, M., Laningham, F. al. (2004). White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor. Journal of Clinical Oncology, 22, 4551–60.
Goldman, M. L., Briery, B., Ward, M. W., Delgado, I. & Armstrong, F. D. (in press). Neurocognitive and educational outcomes of childhood cancer: A longitudinal study. Abstract. Journal of the International Neuropsychological Society.
Hays, D. M., Landsverk, J., Sallan, S. al. (1992). Educational, occupational, and insurance status of childhood cancer survivors in their fourth and fifth decades of life. Journal of Clinical Oncology, 10, 1397–406.
Individuals with Disabilities Education Improvement Act, as amended in 2004, 20 U.S.C. § 1400 et seq.
Katz, E. R., Rubenstein, C. L., Hubert, N. & Blew, A. (1988). School and social reintegration of children with cancer. Journal of Psychosocial Oncology, 6, 123–39.
Katz, E. R., Varni, J. W., Rubenstein, C. L., Blew, A. & Hubert, N. (1992). Teacher, parent, and child evaluative ratings of a school reintegration intervention for children with newly diagnosed cancer. Children's Health Care, 21, 69–75.
Kazak, A. E. (2005). Evidence-based interventions for survivors of childhood cancer and their families. Journal of Pediatric Psychology, 30, 29–39.
Kazak, A. E., Alderfer, M. A., Barakat, L. al. (2004 a). Treatment of posttraumatic stress symptoms in adolescent survivors of childhood cancer and their families: A randomized clinical trial. Journal of Family Psychology, 18, 483–504.
Kazak, A. E., Alderfer, M. A., Rourke, M. al. (2004 b). Posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) in families of adolescent childhood cancer survivors. Journal of Pediatric Psychology, 29, 211–19.
Kazak, A. E., Barakat, L. P., Alderfer, M. al. (2001). Posttraumatic stress in survivors of childhood cancer and mothers: Development and validation of the Impact of Traumatic Stressors Interview Schedule (ITSIS). Journal of Clinical Psychology in Medical Settings, 8, 307–23.
Kazak, A. E., Simms, S., Barakat, al. (1999). Surviving Cancer Competently Intervention Program (SCCIP): A cognitive-behavioral and family therapy intervention for adolescent survivors of childhood cancer and their families. Family Process, 38, 175–91.
Keene, N. (2003). Educating the child with cancer: A guide for parents and teachers. (Available from the Candlelighters Childhood Cancer Foundation,
Mabbott, D. J., Spiegler, B. J., Greenberg, M. al. (2005). Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood. Journal of Clinical Oncology, 23, 2256.
Margolin, J. & Poplack, D. (1997). Acute lymphoblastic leukemia. In Pizzo, P. A. & Poplack, D. G., eds., Principles and Practice of Pediatric Oncology, 3rd edn. Philadelphia: Lippincott-Raven, pp. 409–62.
Merchant, T. E., Mulhern, R. K., Krasin, M. al. (2004). Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma. Journal of Clinical Oncology, 22, 3156–62.
Mitby, P. A., Robison, L. L., Whitton, J. al. (2003). Utilization of special education services and educational attainment among long-term survivors of childhood cancer. Cancer, 97, 1115–26.
Moore, B. D. (2005). Neurocognitive outcomes in survivors of childhood cancer. Journal of Pediatric Psychology, 30, 51–63.
Morris, R. D., Krawiecki, N. S., Kullgren, K. S., Ingram, S. M. & Kurczynski, B. (2000). Brain tumors. In Yeates, K. O., Ris, M. D. & Talyor, H. G., eds., Pediatric neuropsychology: Research, theory, and practice. New York: Guilford Press, pp. 74–91.
Mulhern, R. K., Armstrong, F. D. & Thompson, S. J. (1998). Function-specific neuropsychological assessment. Medical and Pediatric Oncology(Suppl 1), 34–40.
Mulhern, R. K., Carpentieri, S., Shema, S., Stone, P. & Fairclough, D. (1993). Factors associated with social and behavioral problems among children recently diagnosed with brain tumor. Journal of Pediatric Psychology, 18, 339–50.
Mulhern, R. K., Khan, R. B., Kaplan, al. (2005). Short-term efficacy of methylphenidate: A randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. Journal of Clinical Oncology, 22, 4795–803.
Mulhern, R. K., Merchant, T. E., Gajjar, A., Reddick, W. E. & Kun, L. E. (2004 a). Late neurocognitive sequelae in survivors of brain tumours in childhood. The Lancet, 5, 399–408.
Mulhern, R. K., Palmer, S. L., Reddick, W. al. (2001). Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. Journal of Clinical Oncology, 19, 472–9.
Mulhern, R. K., Reddick, W. E., Palmer, S. al. (1999). Neurocognitive deficits in medulloblastoma survivors and white matter loss. Annals of Neurology, 46, 834–41.
Mulhern, R. K., White, H. A., Glass, J. al. (2004 b). Attentional functioning and white matter integrity among survivors of malignant brain tumors of childhood. Journal of the International Neuropsychological Society, 10, 180–9.
National Cancer Institute Research on Childhood Cancers. (2002). Cancer Facts, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Retrieved November 8, 2005 from
Palmer, S. L., Gajjar, A., Reddick, W. al. (2003). Predicting intellectual outcome among children treated with 35–40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology, 17, 548–55.
Penkman, L. (2004). Remediation of attention deficits in children: A focus on childhood cancer, traumatic brain injury and attention deficit disorder. Pediatric Rehabilitation, 7, 111–23.
Poggi, G., Liscio, M., Galbiati, al. (2005). Brain tumors in children and adolescents: Cognitive and psychological disorders at different ages. Psycho-Oncology, 14, 386–95.
Prevatt, F. F., Heffer, R. W. & Lowe, P. A. (2000). A review of school reintegration programs for children with cancer. Journal of School Psychology, 38, 447–67.
Reddick, W. E., White, H. A., Glass, J. al. (2003). Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors. Cancer, 9, 2512–19.
Ries, L. A. G., Eisner, M. P., Kosary, C. L. et al., eds. (2004). SEER Cancer Statistics Review, 1975–2001. Bethesda, MD: National Cancer Institute.
Ris, M. D. & Nortz, M. J. (in press). Nonverbal learning disorders. In Morgan, J. & Ricker, J., eds., Handbook of clinical neuropsychology. Lisse, Netherlands: Swets & Zeitlinger Publishers.
Ris, M. D., Packer, R., Goldwein, J., Jones-Wallace, D. & Boyett, J. M (2001). Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastomas: A children's cancer group study. Journal of Clinical Oncology, 19, 3470–6.
Rynard, D. W., Chambers, A., Klinck, A. M. & Gray, J. D. (1998). School support programs for chronically ill children: Evaluating the adjustment of children with cancer at school. Children's Health Care, 27, 31–46.
Sahler, O. J. Z., Phipps, S., Mulhern, R. al. (2005). Using problem-solving skills training to reduce negative affectivity in mothers of children with newly diagnosed cancer: Report of a multisite randomized trial. Journal of Consulting and Clinical Psychology, 73, 272–83.
Sahler, O. J. Z., Varni, J. W., Fairclough, D. al. (2002). Problem-solving skills training for mothers of children with newly diagnosed cancer: A randomized trial. Journal of Developmental & Behavioral Pediatrics, 23, 77–87.
Schatz, J., Kramer, J. H., Ablin, A. & Matthay, K. K. (2000). Processing speed, working memory, and IQ: A developmental model of cognitive deficits following cranial radiation therapy. Neuropsychology, 14, 189–200.
Sklar, C. A. (2002). Childhood brain tumors. Journal of Pediatric Endocrinology & Metabolism, 15, 669–73.
Spiegler, B. J., Bouffet, E., Greenberg, M. L., Rutka, J. T. & Mabbott, D. J. (2004). Change in neurocognitive functioning after treatment with cranial radiation in childhood. Journal of Clinical Oncology, 22, 706–12.
Streisand, R., Kazak, A. E. & Tercyak, K. P. (2003). Pediatric-specific parenting stress and family functioning in parents of children treated for cancer. Children's Health Care, 32, 245–56.
Teeter, P. A. & Semrud-Clikeman, M. (1995). Integrating neurobiological, psychosocial, and behavioral paradigms: A transactional model for the study of ADHD. Archives of Clinical Neuropsychology, 10, 433–61.
Teeter, P. A. & Semrud-Clikeman, M. (1997). Child neuropsychology: Assessment and interventions for neurodevelopmental disorders. Needham Heights, MA: Allyn & Bacon.
Thompson, S. J., Leigh, L., Christensen, al. (2001). Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer. Journal of Clinical Oncology, 19, 1802–8.
Thomson, J., Kerns, K., Seidenstrang, L., Sohlberg, M. M. & Mateer, C. A. (2001). Pay Attention! A children's attention process training program. Wake Forest, NC: Lash & Associates Publishing.
Treiber, F. A., Schramm, L. & Mabe, P. A. (1986). Children's knowledge and concerns towards a peer with cancer: A workshop intervention approach. Child Psychiatry and Human Development, 16, 38–44.
Varni, J. W., Katz, E. R., Colegrove, R. Jr. & Dolgin, M. (1993). The impact of social skills training on the adjustment of children with newly diagnosed cancer. Journal of Pediatric Psychology, 18, 751–67.
Waber, D. P. & Mullenix, P. J. (2000). Acute lymphoblastic leukemia. In Yeates, K. O., Ris, M. D. & Taylor, H. G., eds. Pediatric neuropsychology: Research, theory, and practiceNew York: Guilford, pp. 300–19.
Wade, S. L., Wolfe, C. R. & Pestian, J. P. (2004). A web-based family problem-solving intervention for families of children with traumatic brain injury. Behavior Research Methods, Instruments & Computers, 36, 261–9.
Yeates, K. O., Taylor, H. G., Barry, C. al. (2001). Neurobehavioral symptoms in childhood closed-head injuries: Changes in prevalence and correlates during the first year postinjury. Journal of Pediatric Psychology, 26, 79–91.