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  • Print publication year: 2008
  • Online publication date: August 2009

14 - Childhood brain tumors


In long-term survivors of childhood and adolescent central nervous system (CNS) tumors, neuropsychological and psychosocial late effects of therapy occur in a milieu of numerous medical late complications (Anderson et al., 2001). With improvements in treatment and survival rates for these patients since the 1980s, most children and adolescents with CNS tumors currently diagnosed will become long-term survivors (Pollack, 1994). This is particularly true for children with medulloblastoma or low-grade astrocytoma. Therefore, concerns about late complications of therapy are increasingly important to survivors and their families. In addition to the late consequences of radiation therapy and chemotherapy, which are similar for all survivors of childhood cancer, the singular susceptibility of the brain and spinal cord to injury causes several late consequences unique to long-term survivors of CNS tumors.

Late complications may be due to the tumor, surgery, radiation therapy, chemotherapy, or the psychological trauma of dealing with a malignancy, and the late effects following CNS tumors include medical, psychological, neuropsychological, and psychosocial problems. Some late effects may be life threatening. In fact, long-term survivors of CNS tumors have an excess risk of mortality relative to survivors of other cancers (Mostow et al., 1991; Nicholson et al., 1994). In a large cohort study of childhood cancer survivors (Oeffinger et al., 2006), CNS tumor survivors were among the most likely to have chronic health conditions and multiple other chronic conditions; in addition, they often have functional impairments (Ness et al., 2005).

Anderson, DM, Rennie, KM, Ziegler, RSet al. (2001). Medical and neurocognitive late effects among survivors of childhood central nervous system tumors. Cancer 92(10): 2709–2719.
Anderson, VA, Godber, T, Smibert, Eet al. (2000). Cognitive and academic outcome following cranial irradiation and chemotherapy in children: a longitudinal study. Br J Cancer 82(2): 255–262.
Bassal, M, Mertens, AC, Taylor, Let al. (2006). Risk of selected subsequent carcinomas in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 24(3): 476–483.
Beebe, DW, Ris, MD, Armstrong, FDet al. (2005). Cognitive and adaptive outcome in low-grade pediatric cerebellar astrocytomas: evidence of diminished cognitive and adaptive functioning in National Collaborative Research Studies (CCG 9891/POG 9130). J Clin Oncol 23(22): 5198–5204.
Bordeaux, JD, Dowell, RE, Copeland, DRet al. (1988). A prospective study of neuropsychological sequelae in children with brain tumors. J Child Neurol 3(1): 63–68.
Bowers, DC, Mulne, AF, Reisch, JSet al. (2002). Nonperioperative strokes in children with central nervous system tumors. Cancer 94: 1094–1101.
Bowers, DC, Liu, Y, Leisenring, Wet al. (2006). Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol 24(33): 5277–5282.
Brownstein, CM, Mertens, AC, Mitby, PAet al. (2004). Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: a report from the childhood cancer survivor study. J Clin Endocrinol Metab 89(9): 4422–4427.
Buono, L, Morris, M, Morris, Ret al. (1998). Evidence for the syndrome of nonverbal learning disabilities in children with brain tumors. Child Neuropsychol 4(2): 144–157.
Butler, RW, Copeland, DR (2002). Attentional processes and their remediation in children treated for cancer: a literature review and the development of a therapeutic approach. J Int Neuropsychol Soc 8(1): 115–124.
Butler, RW, Mulhern, RK (2005). Neurocognitive interventions for children and adolescents surviving cancer. J Pediatr Psychol 30(1): 65–78.
Butler, RW, Hill, JM, Steinherz, PGet al. (1994). Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer. J Clin Oncol 12(12): 2621–2629.
Carlson-Green, B, Morris, RD, Krawiecki, N (1995). Family and illness predictors of outcome in pediatric brain tumors. J Pediatr Psychol 20(6): 769–784.
Copeland, DR, deMoor, C, Moore, BD 3rd et al. (1999). Neurocognitive development of children after a cerebellar tumor in infancy: a longitudinal study. J Clin Oncol 17(11): 3476–3486.
Daugaard, G, Abildgaard, U (1991). Renal Morbidity of Chemotherapy. Oxford: Butterworth-Heinemann.
Donaldson, SS, Kaplan, HS (1982). Complications of treatment of Hodgkin's disease in children. Cancer Treat Rep 66(4): 977–989.
Eiser, C (2004). Neurocognitive sequelae of childhood cancers and their treatment: a comment on Mulhern and Butler. Pediatr Rehabil 7(1): 15–16.
Ellenberg, L, McComb, JG, Siegel, SEet al. (1987). Factors affecting intellectual outcome in pediatric brain tumor patients. Neurosurgery 21(5): 638–644.
Ergun-Longmire, B, Mertens, AC, Mitby, Pet al. (2006). Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab 91(9): 3494–3498.
Filley, CM (2001). The Behavioral Neurology of White Matter. New York: Oxford University Press.
Fletcher, JM, Copeland, DR (1988). Neurobehavioral effects of central nervous system prophylactic treatment of cancer in children. J Clin Exp Neuropsychol 10(4): 495–537.
Fuemmeler, BF, Elkin, TD, Mullins, LL (2002). Survivors of childhood brain tumors: behavioral, emotional, and social adjustment. Clin Psychol Rev 22(4): 547–585.
Goldstein, AM, Pastakia, B, DiGiovanna, JJet al. (1994). Clinical findings in two African-American families with the nevoid basal cell carcinoma syndrome (NBCC). Am J Med Genet 50(3): 272–281.
Goldstein, AM, Yuen, J, Tucker, MA (1997). Second cancers after medulloblastoma: population-based results from the United States and Sweden. Cancer Causes Control 8(6): 865–871.
Gurney, J, Kadan-Lottick, N, Packer, Ret al. (2003a). Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer 97: 663–673.
Gurney, JG, Ness, KK, Stovall, Met al. (2003b). Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study. J Clin Endocrinol Metab 88(10): 4731–4739.
Hamilton, , Liu, B, Parsons, REet al. (1995). The molecular basis of Turcot's syndrome. N Engl J Med 332(13): 839–847.
Hancock, SL, Cox, RS, McDougall, IR (1991). Thyroid diseases after treatment of Hodgkin's disease. N Engl J Med 325(9): 599–605.
Heikens, J, Ubbink, M, Pal, Het al. (2000). Long term survivors of childhood brain cancer have an increased risk for cardiovascular disease. Cancer 88: 2116–2121.
Hoppe-Hirsch, E, Renier, D, Lellouch-Tubiana, Aet al. (1990). Medulloblastoma in childhood: progressive intellectual deterioration. Childs Nerv Syst 6(2): 60–65.
Hoppe-Hirsch, E, Brunet, L, Laroussinie, Fet al. (1995). Intellectual outcome in children with malignant tumors of the posterior fossa: influence of the field of irradiation and quality of surgery. Childs Nerv Syst 11(6): 340–345; discussion 345–346.
Jakacki, RI, Goldwein, JW, Larsen, RLet al. (1993). Cardiac dysfunction following spinal irradiation during childhood. J Clin Oncol 11(6): 1033–1038.
Jakacki, RI, Schramm, CM, Donahue, BRet al. (1995). Restrictive lung disease following treatment for malignant brain tumors: a potential late effect of craniospinal irradiation. J Clin Oncol 13(6): 1478–1485.
Jankovic, M, Brouwers, P, Valsecchi, MGet al. (1994). Association of 1800 cGy cranial irradiation with intellectual function in children with acute lymphoblastic leukaemia. ISPACC. International Study Group on Psychosocial Aspects of Childhood Cancer. Lancet 344(8917): 224–227.
Jannoun, L, Bloom, HJ (1990). Long-term psychological effects in children treated for intracranial tumors. Int J Radiat Oncol Biol Phys 18(4): 747–753.
Kleinschmidt-DeMasters, BK, Lillehei, KO (1995). Radiation-induced meningioma with a 63-year latency period. Case report. J Neurosurg 82(3): 487–488.
Kramer, S, Lee, KF (1974). Complications of radiation therapy: the central nervous system. Semin Roentgenol 9(1): 75–83.
Landier, W, Bhatia, S, Eshelman, DAet al. (2004). Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committe and Nursing Discipline. J Clin Oncol 22(24): 4979–4990.
Lipshultz, SE, Colan, SD, Gelber, RDet al. (1991). Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 324(12): 808–815.
Luban, NL (1998). An update on transfusion-transmitted viruses. Curr Opin Pediatr 10(1): 53–59.
Mabbott, D, Penkman, L, Witol, Aet al. (2005). Attention, working memory and processing speed in children with posterior fossa tumours. Poster presented at the 2005 International Neuropsychological Society Meeting, Dublin, Ireland, 6–9 July, 2005.
Martins, AN, Johnston, JS, Henry, JMet al. (1977). Delayed radiation necrosis of the brain. J Neurosurg 47(3): 336–345.
Mertens, AC, Yasui, Y, Neglia, JPet al. (2001). Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J Clin Oncol 19(13): 3163–3172.
Mertens, AC, Yasui, Y, Liu, Yet al. (2002). Pulmonary complications in survivors of childhood and adolescent cancer. A report from the Childhood Cancer Survivor Study. Cancer 95(11): 2431–2441.
Mostow, EN, Byrne, J, Connelly, RRet al. (1991). Quality of life in long-term survivors of CNS tumors of childhood and adolescence. J Clin Oncol 9(4): 592–599.
Mulhern, RK, Butler, RW (2004). Neurocognitive sequelae of childhood cancers and their treatment. Pediatr Rehabil 7(1): 1–14; discussion 15–16.
Mulhern, R, Butler, RW (2005). Neuropsychological late effects. In Brown, RT (ed.) Pediatric Hematology/Oncology: A Biopsychosocial Approach. New York: Oxford University Press.
Mulhern, RK, Wasserman, AL, Friedman, AGet al. (1989). Social competence and behavioral adjustment of children who are long-term survivors of cancer. Pediatrics 83(1): 18–25.
Mulhern, RK, Hancock, J, Fairclough, Det al. (1992). Neuropsychological status of children treated for brain tumors: a critical review and integrative analysis. Med Pediatr Oncol 20(3): 181–191.
Mulhern, RK, Kepner, JL, Thomas, PRet al. (1998). Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study. J Clin Oncol 16(5): 1723–1728.
Mulhern, RK, Reddick, WE, Palmer, SL (1999). Neurocognitive deficits in medulloblastoma survivors and white matter loss. Ann Neurol 46(6): 834–841.
Mulhern, R, Palmer, S, Reddick, Wet al. (2001). Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. J Clin Oncol 19(2): 472–479.
Mulhern, RK, White, HA, Glass, JOet al. (2004). Attentional functioning and white matter integrity among survivors of malignant brain tumors of childhood. J Int Neuropsychol Soc 10(2): 180–189.
Neglia, JP, Robison, LL, Stovall, Met al. (2006). New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98(21): 1528–1537.
Ness, KK, Mertens, AC, Hudson, MMet al. (2005). Limitations on physical performance and daily activities among long-term survivors of childhood cancer. Ann Intern Med 143(9): 639–647.
Nicholson, HS, Butler, R (2001). Late effects of therapy in long-term survivors. In Keating, R, Goodrich, J, Packer, R (eds.) Tumors of the Pediatric Central Nervous System. New York: Thieme.
Nicholson, HS, Fears, TR, Byrne, J (1994). Death during adulthood in survivors of childhood and adolescent cancer. Cancer 73(12): 3094–3102.
Oberfield, SE, Soranno, D, Nirenberg, Aet al. (1996). Age at onset of puberty following high-dose central nervous system radiation therapy. Arch Pediatr Adolesc Med 150(6): 589–592.
O'Driscoll, BR, Hasleton, PS, Taylor, PMet al. (1990). Active lung fibrosis up to 17 years after chemotherapy with carmustine (BCNU) in childhood. N Engl J Med 323(6): 378–382.
Oeffinger, KC, Mertens, AC, Hudson, MMet al. (2004). Health care of young adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Fam Med 2(1): 61–70.
Oeffinger, KC, Mertens, AC, Sklar, CAet al. (2006). Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355(15): 1572–1582.
Packer, RJ, Sutton, LN, Atkins, TEet al. (1989). A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70(5): 707–713.
Packer, RJ, Sutton, LN, Elterman, Ret al. (1994). Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg 81(5): 690–698.
Packer, R, Gurney, J, Punyko, Jet al. (2003). Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: Childhood Cancer Survivor Study. J Clin Oncol 21: 3255–3261.
Palmer, SL, Goloubeva, O, Reddick, WEet al. (2001). Patterns of intellectual development among survivors of pediatric medulloblastoma: a longitudinal analysis. J Clin Oncol 19(8): 2302–2308.
Palmer, SL, Gajjar, A, Reddick, WEet al. (2003). Predicting intellectual outcome among children treated with 35–40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology 17(4): 548–555.
Penkman, L (2004). Remediation of attention deficits in children: a focus on childhood cancer, traumatic brain injury and attention deficit disorder. Pediatr Rehabil 7(2): 111–123.
Peterson, K, Shao, C, McCarter, Ret al. (2005). An analysis of SEER data of increasing risk of secondary malignant neoplasms among long-term survivors of childhood brain tumors. Pediatric Blood Cancer 47: 83–88.
Pollack, IF (1994). Brain tumors in children. N Engl J Med 331(22): 1500–1507.
Radcliffe, J, Packer, RJ, Atkins, TEet al. (1992). Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy. Ann Neurol 32(4): 551–554.
Reddick, WE, White, HA, Glass, JOet al. (2003). Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors. Cancer 97(10): 2512–2519.
Reddick, WE, Glass, JO, Palmer, SLet al. (2005). Atypical white matter volume development in children following craniospinal irradiation. Neurooncology 7(1): 12–19.
Reeves, CB, Palmer, SL, Reddick, WEet al. (2006). Attention and memory functioning among pediatric patients with medulloblastoma. J Pediatr Psychol 31: 272–280.
Reimers, TS, Ehrenfels, S, Mortensen, ELet al. (2003). Cognitive deficits in long-term survivors of childhood brain tumors: identification of predictive factors. Med Pediatr Oncol 40(1): 26–34.
Reinhold, HS, Calvo, W, Hopewell, JWet al. (1990). Development of blood vessel-related radiation damage in the fimbria of the central nervous system. Int J Radiat Oncol Biol Phys 18(1): 37–42.
Ries, LAG, Eisner, M, Kosary, Cet al. (2005). SEER Cancer Statistics Review, 1975–2002. Bethesda, MD: National Cancer Institute., based on November 2004 SEER data submission, posted to the SEER website, 2005.
Ris, MD, Noll, RB (1994). Long-term neurobehavioral outcome in pediatric brain-tumor patients: review and methodological critique. J Clin Exp Neuropsychol 16(1): 21–42.
Ris, MD, Packer, R, Goldwein, Jet al. (2001). Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study. J Clin Oncol 19(15): 3470–3476.
Riva, D, Pantaleoni, C, Milani, Net al. (1989). Impairment of neuropsychological functions in children with medulloblastomas and astrocytomas in the posterior fossa. Childs Nerv Syst 5(2): 107–110.
Ronckers, CM, Sigurdson, AJ, Stovall, Met al. (2006). Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers. Radiat Res 166(4): 618–628.
Ross, L, Johansen, C, Dalton, Set al. (2003). Psychiatric hospitalizations among survivors of cancer in childhood or adolescence. New Engl J Med 349: 650–657.
Shuper, A, Packer, RJ, Vezina, LGet al. (1995). “Complicated migraine-like episodes” in children following cranial irradiation and chemotherapy. Neurology 45(10): 1837–1840.
Skinner, R, Pearson, AD, Amineddine, HAet al. (1990). Ototoxicity of cisplatinum in children and adolescents. Br J Cancer 61(6): 927–931.
Sklar, CA (1995). Growth following therapy for childhood cancer. Cancer Invest 13(5): 511–516.
Sklar, CA (1997). Growth and neuroendocrine dysfunction following therapy for childhood cancer. Pediatr Clin North Am 44(2): 489–503.
Sklar, CA, Constine, LS (1995). Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31(5): 1113–1121.
Stavrou, T, Bromley, C, Nicholson, HSet al. (2001). Prognostic factors and secondary malignancies in childhood medulloblastoma. J Pediatr Hematol Oncol 23: 431–436.
Strother, D, Pollack, I, Fisher, PGet al. (2002). Tumors of the central nervous system. In Poplack, PA (ed.) Principles and Practice of Pediatric Oncology (4th edn.). Philadelphia, PA: Lippincott Williams & Wilkins.
Travis, LB, Rabkin, CS, Brown, LMet al. (2006). Cancer survivorship – genetic susceptibility and second primary cancers: research strategies and recommendations. J Natl Cancer Inst 98(1): 15–25.
Vassilopoulou, S, Klein, MJ, Moore, BDet al. (1995). Efficacy of growth hormone replacement therapy in children with organic growth hormone deficiency after cranial irradiation. Horm Res 43(5): 188–193.
Walter, AW, Mulhern, RK, Gajjar, Aet al. (1999). Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children's Research Hospital. J Clin Oncol 17(12): 3720–3728.
Yeates, KO, Swift, E, Taylor, HGet al. (2004). Short- and long-term social outcomes following pediatric traumatic brain injury. J Int Neuropsychol Soc 10(3): 412–426.