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Neuropsychological Late Effects of Radiotherapy for Pediatric Brain Tumors

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Radiation Oncology for Pediatric CNS Tumors

Abstract

Advances in the treatment of pediatric brain tumors have led to an overall increase in survival rates, which in turn has led to increased identification of physical, cognitive, academic/vocational, and socioemotional sequelae among survivors. Research to date has shown radiotherapy to account for a significant amount of variance in neurocognitive outcomes. However, other predisposing factors have also been identified, and research into the relative role of the direct and indirect effects of medical, child-specific, and broader contextual/environmental factors on outcomes in this population is needed. This chapter describes our current knowledge of neuropsychological and associated functional outcomes among survivors of pediatric brain tumor as well as the current literature on associated predisposing factors, pathophysiology, and evidence-based interventions for remediation and prevention. Methodological issues are also discussed in order to provide context for understanding limitations of current findings and to identify important future directions.

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References

  • Anderson VA, Godber T, Smibert E et al (2000) Cognitive and academic outcome following cranial irradiation and chemotherapy in children: a longitudinal study. Br J Cancer 82(2):255–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Annett RD, Patel SK, Phipps S (2015) Monitoring and assessment of neuropsychological outcomes as a standard of care in pediatric oncology. Pediatr Blood Cancer 62(Suppl 5):S460–S513

    Article  PubMed  Google Scholar 

  • Ashford JM, Netson KL, Clark KN et al (2014) Adaptive functioning of childhood brain tumor survivors following conformal radiation therapy. J Neuro-Oncol 118(1):193–199

    Article  Google Scholar 

  • Barakat LP, Hetzke JD, Foley B et al (2003) Evaluation of a social-skills training group intervention with children treated for brain tumors: a pilot study. J Pediatr Psychol 28(5):299–307

    Article  PubMed  Google Scholar 

  • Barrera M, Shaw AK, Speechley KN et al (2005) Educational and social late effects of childhood cancer and related clinical, personal, and familial characteristics. Cancer 104(8):1751–1760

    Article  PubMed  Google Scholar 

  • Beebe DW, Ris MD, Armstrong FD et 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

    Article  PubMed  Google Scholar 

  • Beek L, Schappin R, Gooskens R et al (2015) Surviving a brain tumor in childhood: impact on family functioning in adolescence. Psycho-Oncology 24(1):89–94

    Article  PubMed  Google Scholar 

  • Benner AE, Marlow LS (1991) The effect of a workshop on childhood cancer on students’ knowledge, concerns, and desire to interact with a classmate with cancer. Child Health Care 20:101–107

    Article  Google Scholar 

  • Blackmore DG, Golmohammadi MG, Large B et al (2009) Exercise increases neural stem cell number in a growth hormone-dependent manner, augmenting the regenerative response in aged mice. Stem Cells 27(8):2044–2052

    Article  CAS  PubMed  Google Scholar 

  • Brinkman TM, Palmer SL, Chen S et al (2012) Parent-reported social outcomes after treatment for pediatric embryonal tumors: a prospective longitudinal study. J Clin Oncol 30(33):4134–4140

    Article  PubMed  PubMed Central  Google Scholar 

  • Brinkman TM, Liptak CC, Delaney BL et al (2013a) Suicide ideation in pediatric and adult survivors of childhood brain tumors. J Neurooncol 113(3):425–432

    Article  PubMed  Google Scholar 

  • Brinkman TM, Ullrich NJ, Zhang N et al (2013b) Prevalence and predictors of prescription psychoactive medication use in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Cancer Surviv 7(1):104–114

    Article  PubMed  Google Scholar 

  • Brinkman TM, Zhang N, Ullrich NJ et al (2013c) Psychoactive medication use and neurocognitive function in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor study. Pediatr Blood Cancer 60(3):486–493

    Article  PubMed  Google Scholar 

  • Butler RW (1998) Attentional processes and their remediation in childhood cancer. Med Pediatr Oncol 30(Suppl 1):75–78

    Article  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Butler RW, Copeland DR, Fairclough DL et al (2008) A multicenter, randomized clinical trial of a cognitive remediation program for childhood survivors of a pediatric malignancy. J Consult Clin Psychol 76(3):367–378

    Article  PubMed  PubMed Central  Google Scholar 

  • Carrie C, Grill J, Figarella-Branger D et al (2009) Online quality control, hyperfractionated radiotherapy alone and reduced boost volume for standard risk medulloblastoma: long-term results of MSFOP 98. J Clin Oncol 27(11):1879–1883

    Article  PubMed  Google Scholar 

  • Castellino SM, Tooze JA, Flowers L et al (2012) Toxicity and efficacy of the acetylcholinesterase (AChe) inhibitor donepezil in childhood brain tumor surivivors: a pilot study. Pediatr Blood Cancer 59(3):540–547

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheung LL, Wakefield CE, Ellis SJ et al (2014) Neuropsychology reports for childhood brain tumor survivors: implementation of recommendations at home and school. Pediatr Blood Cancer 61(6):1080–1087

    Article  PubMed  Google Scholar 

  • Children’s Oncology Group (2013) Long-term follow-up guidelines for survivors of childhood, adolescent and young adult cancers, version 4.0. Monrovia, CA: Children’s Oncology Group. www.survivorshipguidelines.org. Accessed 5 Apr 2016

  • Cole PD, Finkelstein Y, Stevenson KE et al (2015) Polymorphisms in genes related to oxidative stress are associated with inferior cognitive function after therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 33(19):2205–2211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conklin HM, Khan RB, Reddick WE et al (2007) Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial. J Pediatr Psychol 32(9):1127–1139

    Article  PubMed  Google Scholar 

  • Conklin HM, Li C, Xiong X et al (2008) Predicting change in academic abilities after conformal radiation therapy for localized ependymoma. J Clin Oncol 26(24):3965–3970

    Article  PubMed  PubMed Central  Google Scholar 

  • Conklin HM, Lawford J, Jasper BW et al (2009) Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial. Pediatrics 124(1):226–233

    Article  PubMed  PubMed Central  Google Scholar 

  • Conklin HM, Helton S, Ashford J et al (2010a) Predicting methylphenidate response in long-term survivors of childhood cancer: a randomized, double-blind, placebo-controlled, crossover trial. J Pediatr Psychol 35(2):144–155

    Article  PubMed  Google Scholar 

  • Conklin HM, Reddick WE, Ashford J et al (2010b) Long-term efficacy of methylphenidate in enhancing attention regulation, social skills, and academic abilities of childhood cancer survivors. J Clin Oncol 28(29):4465–4472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conklin HM, Ashford JM, Howarth RA et al (2012) Working memory performance among childhood brain tumor survivors. J Int Neuropsychol Soc 18(6):996–1005

    Article  PubMed  PubMed Central  Google Scholar 

  • Conklin HM, Ashford JM, Di Pinto M et al (2013) Computerized assessment of cognitive late effects among adolescent brain tumor survivors. J Neuro-Oncol 113(2):333–340

    Article  Google Scholar 

  • Conklin HM, Ogg RJ, Ashford JM et al (2015) Computerized cognitive training for amelioration of cognitive late effects among childhood cancer survivors: a randomized controlled trial. J Clin Oncol 33(33):3894–3902

    Article  PubMed  PubMed Central  Google Scholar 

  • Correa DD, Satagopan J, Baser RE et al (2014) APOE polymorphisms and cognitive functions in patients with brain tumors. Neurology 83(4):320–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox LE, Ashford JM, Clark KN et al (2015) Feasibility and acceptability of a remotely administered computerized intervention to address cognitive late effects among childhood cancer survivors. Neurooncol Pract 2(2):78–87

    PubMed  PubMed Central  Google Scholar 

  • Crosby AE, Han B, Ortega LAG et al (2011) Suicidal thoughts and behaviors among adults aged ≥18 years-United States, 2008-2009. MMWR Surveill Summ 60(13):1–22

    PubMed  Google Scholar 

  • de Blank PMK, Berman JI, Fisher MJ (2016) Systemic chemotherapy and white matter integrity in tracts associated with cognition among children with neurofibromatosis type 1. Pediatr Blood Cancer 63:818–824

    Article  PubMed  Google Scholar 

  • de Boer AG, Verbeek JH, Van Dijk FJ (2006) Adult survivors of childhood cancer and unemployment: a metaanalysis. Cancer 107(1):1–11

    Article  PubMed  Google Scholar 

  • de Ruiter MA, Van Mourik R, Schouten-Van Meeteren AY et al (2013) Neurocognitive consequences of a paediatric brain tumour and its treatment: a meta-analysis. Dev Med Child Neurol 55(5):408–417

    Article  PubMed  Google Scholar 

  • Deyell RJ, Lorenzi M, Ma S et al (2013) Antidepressant use among survivors of childhood, adolescent and young adult cancer: a report of the Childhood, Adolescent and Young Adult Cancer Survivor (CAYACS) Research Program. Pediatr Blood Cancer 60(5):816–822

    Article  PubMed  Google Scholar 

  • Di Pinto M, Conklin HM, Li C et al (2012) Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 84(3):e363–e369

    Article  PubMed  PubMed Central  Google Scholar 

  • Ellenberg L, McComb JG, Siegel SE et al (1987) Factors affecting intellectual outcome in pediatric brain tumor patients. Neurosurgery 21(5):638–644

    Article  CAS  PubMed  Google Scholar 

  • Farjam R, Pramanik P, Aryal MP et al (2015) A radiation-induced hippocampal vascular injury surrogate marker predicts late neurocognitive dysfunction. Int J Radiat Oncol Biol Phys 93(4):908–915

    Article  PubMed  PubMed Central  Google Scholar 

  • Fouladi M, Chintagumpala M, Laningham FH et al (2004) White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 22(22):4551–4560

    Article  PubMed  Google Scholar 

  • Fry AF, Hale S (1996) Processing speed, working memory, and fluid intelligence: evidence for a developmental cascade. Psychol Sci 7:237–241

    Article  Google Scholar 

  • Gan L, Wang ZH, Zhang H et al (2015) Protective effects of shikonin on brain injury induced by carbon ion beam irradiation in mice. Biomed Environ Sci 28(2):148–151

    PubMed  Google Scholar 

  • Gondi V, Hermann BP, Mehta MP, Tomé WA (2012) Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 83(4):e487–e493

    Article  PubMed  Google Scholar 

  • Gondi V, Pugh SL, Tome WA et al (2014) Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 32(34):3810–3816

    Article  PubMed  PubMed Central  Google Scholar 

  • Greenberger BA, Pulsifer MB, Ebb DH et al (2014) Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas. Int J Radiat Oncol Biol Phys 89(5):1060–1068

    Article  PubMed  Google Scholar 

  • Handschin C, Spiegelman BM (2008) The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 454(7203):463–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardy KK, Willard VW, Allen TM, Bonner MJ (2013) Working memory training in survivors of pediatric cancer: a randomized pilot study. Psychooncology 22(8):1856–1865

    Article  PubMed  Google Scholar 

  • Holland AA, Hughes CW, Stavinoha PL (2014) School competence and fluent academic performance: informing assessment of educational outcomes in survivors of pediatric medulloblastoma. Appl Neuropsychol Child 14:1–8

    Google Scholar 

  • Holmquist LA, Scott J (2002) Treatment, age, and time-related predictors of behavioral outcome in pediatric brain tumor survivors. J Clin Psychol Med Settings 9(4):315–321

    Article  Google Scholar 

  • Howlader N, Noone AM, Krapcho M et al (eds) (2015) SEER Cancer Statistics Review, 1975–2012, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2012/, based on November 2014 SEER data submission, posted to the SEER web site Apr 2015. Accessed 5 Apr 2016

  • Jacola LM, Ashford JM, Reddick WE et al (2014) The relationship between working memory and cerebral white matter volume in survivors of childhood brain tumors treated with conformal radiation therapy. J Neuro-Oncol 119(1):197–205

    Article  Google Scholar 

  • Jain N, Krull KR, Brouwers P et al (2008) Neuropsychological outcome following intensity-modulated radiation therapy for pediatric medulloblastoma. Pediatr Blood Cancer 51(2):275–279

    Article  PubMed  Google Scholar 

  • Jasper BW, Conklin HM, Lawford J et al (2009) Growth effects of methylphenidate among childhood cancer survivors: a 12-month case-matched open-label study. Pediatr Blood Cancer 52(1):39–43

    Article  PubMed  PubMed Central  Google Scholar 

  • Jayakar R, King TZ, Morris R (2015) Hippocampal volume and auditory attention on a verbal memory task with adult survivors of pediatric brain tumor. Neuropsychology 29(2):303–319

    Article  PubMed  Google Scholar 

  • Jimenez RB, Sethi R, Depauw N et al (2013) Proton radiation therapy for pediatric medulloblastoma and supratentorial primitive neuroectodermal tumors: outcomes for very young children treated with upfront chemotherapy. Int J Radiat Oncol Biol Phys 87(1):120–126

    Article  PubMed  Google Scholar 

  • Kahalley LS, Conklin HM, Tyc VL et al (2011) ADHD and secondary ADHD criteria fail to identify many at-risk survivors of pediatric ALL and brain tumor. Pediatr Blood Cancer 57(1):110–118

    Article  PubMed  PubMed Central  Google Scholar 

  • Kahalley LS, Conklin HM, Tyc VL et al (2013) Slower processing speed after treatment for pediatric brain tumor and acute lymphoblastic leukemia. Psycho-Oncology 22(9):1979–1986

    Article  PubMed  PubMed Central  Google Scholar 

  • Kahalley LS, Ris MD, Grosshans DR et al (2016) Comparing intelligence quotient change after treatment with proton versus photon radiation therapy for pediatric brain tumors. J Clin Oncol 34(10):1043–1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamdar KY, Krull KR, El-Zein RA et al (2011) Folate pathway polymorphisms predict deficits in attention and processing speed after childhood leukemia therapy. Pediatr Blood Cancer 57(3):454–460

    Article  PubMed  PubMed Central  Google Scholar 

  • Kazak AE, Barakat LP, Alderfer M et al (2001) Posttraumatic stress in survivors of childhood cancer and mothers: development and validation of the impact of traumatic stressors interview schedule (ITSIS). J Clin Psychol Med Settings 8(4):307–323

    Article  Google Scholar 

  • Kazak AE, Alderfer M, Rourke MT et al (2004a) Posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) in families of adolescent childhood cancer survivors. J Pediatr Psychol 29(3):211–219

    Article  PubMed  Google Scholar 

  • Kazak AE, Alderfer MA, Streisand R et al (2004b) Treatment of posttraumatic stress symptoms in adolescent survivors of childhood cancer and their families: a randomized clinical trial. J Fam Psychol 18(3):493–504

    Article  PubMed  Google Scholar 

  • Kesler SR, Lacayo NJ, Jo B (2011) A pilot study of an online cognitive rehabilitation program for executive function skills in children with cancer-related brain injury. Brain Inj 25(1):101–112

    Article  PubMed  PubMed Central  Google Scholar 

  • Khong PL, Leung LH, Fung AS et al (2006) White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function. J Clin Oncol 24(6):884–890

    Article  PubMed  Google Scholar 

  • King TZ, Fennell EB, Williams L et al (2004) Verbal memory abilities of children with brain tumors. Child Neuropsychol 10(2):76–88

    Article  PubMed  Google Scholar 

  • Kirchhoff AC, Leisenring W, Krull KR et al (2010) Unemployment among adult survivors of childhood cancer: a report from the childhood cancer survivor study. Med Care 48(11):1015–1025

    Article  PubMed  PubMed Central  Google Scholar 

  • Kirsch DG, Tarbell NJ (2004) New technologies in radiation therapy for pediatric brain tumors: the rationale for proton radiation therapy. Pediatr Blood Cancer 42(5):461–464

    Article  PubMed  Google Scholar 

  • Krull KR, Brouwers P, Jain N et al (2008) Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors. J Pediatr 152(1):101–105

    Article  CAS  PubMed  Google Scholar 

  • Krull KR, Bhojwani D, Conklin HM et al (2013) Genetic mediators of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 31(17):2182–2188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kullgren KA, Morris RD, Morris MK et al (2003) Risk factors associated with long-term social and behavioral problems among children with brain tumors. J Psychosoc Oncol 21(1):73–87

    Article  Google Scholar 

  • Kun LE, Beltran C (2009) Radiation therapy for children: evolving technologies in the era of ALARA. Pediatr Radiol 39(Suppl 1):S65–S70

    Article  PubMed  Google Scholar 

  • Law N, Bouffet E, Laughlin S et al (2011) Cerebello–thalamo–cerebral connections in pediatric brain tumor patients: impact on working memory. NeuroImage 56(4):2238–2248

    Article  PubMed  Google Scholar 

  • Lorenzi M, McMillan AJ, Siegel LS et al (2009) Educational outcomes among survivors of childhood cancer in British Columbia, Canada: report of the Childhood/Adolescent/Young Adult Cancer Survivors (CAYACS) Program. Cancer 115(10):2234–2245

    Article  PubMed  Google Scholar 

  • Lund LW, Winther JF, Cederkvist L et al (2015) Increased risk of antidepressant use in childhood cancer survivors: a Danish population-based cohort study. Eur J Cancer 51(5):675–684

    Article  PubMed  Google Scholar 

  • Mabbott DJ, Spiegler BJ, Greenberg ML et al (2005) Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood. J Clin Oncol 23(10):2256–2263

    Article  PubMed  Google Scholar 

  • Mabbott DJ, Noseworthy MD, Bouffet E et al (2006) Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ. Neuro-Oncology 8(3):244–252

    Article  PubMed  PubMed Central  Google Scholar 

  • Mabbott DJ, Penkman L, Witol A et al (2008) Core neurocognitive functions in children treated for posterior fossa tumors. Neuropsychology 22(2):159–168

    Article  PubMed  Google Scholar 

  • MacDonald SM, Sethi R, Levally B et al (2013) Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients. Neuro-Oncology 15:1552–1559

    Article  PubMed  PubMed Central  Google Scholar 

  • Merchant TE, Mulhern RK, Krasin MJ et 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. J Clin Oncol 22(15):3156–3162

    Article  PubMed  Google Scholar 

  • Miller EK, Cohen JD (2001) An integrative theory of prefrontal cortex function. Annu Rev Neurosci 24(1):167–202

    Article  CAS  PubMed  Google Scholar 

  • Mitby PA, Robison LL, Whitton MA et al (2003) Utilization of special education services and educational attainment among long-term survivors of childhood cancer. Cancer 97:1115–1126

    Article  PubMed  Google Scholar 

  • Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302(5651):1760–1765

    Article  CAS  PubMed  Google Scholar 

  • Moore BD (2005) Neurocognitive outcomes in survivors of childhood cancer. J Pediatr Psychol 30:51–63

    Article  PubMed  Google Scholar 

  • Moore IM, Hockenberry MJ, Anhalt C et al (2012) Mathematics intervention for prevention of neurocognitive deficits in childhood leukemia. Pediatr Blood Cancer 59(2):278–284

    Article  PubMed  Google Scholar 

  • Moxon-Emre I, Bouffet E, Taylor MD et al (2014) Impact of craniospinal dose, boost volume, and neurologic complications on intellectual outcome in patients with medulloblastoma. J Clin Oncol 32(17):1760–1768

    Article  PubMed  Google Scholar 

  • Moyer KH, Willard VW, Gross AM et al (2012) The impact of attention on social functioning in survivors of pediatric acute lymphoblastic leukemia and brain tumors. Pediatr Blood Cancer 59(7):1290–1295

    Article  PubMed  PubMed Central  Google Scholar 

  • Mulhern RK, Palmer SL, Reddick WE et 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

    Article  CAS  PubMed  Google Scholar 

  • Mulhern RK, Khan RB, Kaplan S et al (2004a) Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. J Clin Oncol 22(23):4795–4803

    Article  CAS  PubMed  Google Scholar 

  • Mulhern RK, Merchant TE, Gajjar A et al (2004b) Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet 5:399–408

    Article  PubMed  Google Scholar 

  • Mulhern RK, White HA, Glass JO et al (2004c) Attentional functioning and white matter integrity among survivors of malignant brain tumors of childhood. J Int Neuropsychol Soc 10(2):180–189

    Article  PubMed  Google Scholar 

  • Mulhern RK, Palmer SL, Merchant TE et al (2005) Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol 23(24):5511–5519

    Article  PubMed  Google Scholar 

  • Naylor AS, Bull C, Nilsson MK et al (2008) Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A 105(38):14632–14637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Netson KL, Conklin HM, Ashford JM et al (2011) Parent and teacher ratings of attention during a year-long methylphenidate trial in children treated for cancer. J Pediatr Psychol 36(4):438–450

    Article  PubMed  Google Scholar 

  • Netson KL, Conklin HM, Wu S et al (2012) A 5-year investigation of children’s adaptive functioning following conformal radiation therapy for localized ependymoma. Int J Radiat Oncol Biol Phys 84(1):217–223

    Article  PubMed  PubMed Central  Google Scholar 

  • Netson KL, Conklin HM, Wu S et al (2013) Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 85(5):1301–1306

    Article  PubMed  Google Scholar 

  • Olsson IT, Perrin S, Lundgren J et al (2014) Long-term cognitive sequelae after pediatric brain tumor related to medical risk factors, age, and sex. Pediatr Neurol 51(4):515–521

    Article  Google Scholar 

  • Özyurt J, Thiel CM, Lorenzen A et al (2014) Neuropsychological outcome in patients with childhood craniopharyngioma and hypothalamic involvement. J Pediatr 164(4):876–881

    Article  PubMed  Google Scholar 

  • Palmer SL (2008) Neurodevelopmental impact on children treated for medulloblastoma: a review and proposed conceptual model. Dev Disabil Res Rev 14(3):203–210

    Article  PubMed  PubMed Central  Google Scholar 

  • Palmer SL, Goloubeva O, Reddick WE et al (2001) Patterns of intellectual development among survivors of pediatric medulloblastoma: a longitudinal analysis. J Clin Oncol 19(8):2302–2308

    Article  CAS  PubMed  Google Scholar 

  • Palmer SL, Gajjar A, Reddick WE et al (2003) Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology 17(4):548–555

    Article  PubMed  Google Scholar 

  • Palmer SL, Hassall T, Evankovich K et al (2010) Neurocognitive outcome 12 months following cerebellar mutism syndrome in pediatric patients with medulloblastoma. Neuro-Oncology 12(12):1311–1317

    PubMed  PubMed Central  Google Scholar 

  • Palmer SL, Armstrong C, Onar-Thomas A et al (2013) Processing speed, attention, and working memory after treatment for medulloblastoma: an international, prospective, and longitudinal study. J Clin Oncol 31(28):3494–3500

    Article  PubMed  PubMed Central  Google Scholar 

  • Pang JW, Friedman DL, Whitton JA et al (2008) Employment status among adult survivors in the Childhood Cancer Survivor Study. Pediatr Blood Cancer 50(1):104–110

    Article  PubMed  Google Scholar 

  • Papazoglou A, King TZ, Morris RD et al (2008) Cognitive predictors of adaptive functioning vary according to pediatric brain tumor location. Dev Neuropsychol 33(4):505–520

    Article  PubMed  Google Scholar 

  • Patel SK, Katz ER, Richardson R et al (2009) Cognitive and problem solving training in children with cancer: a pilot project. J Pediatr Hematol Oncol 31(9):670–677

    Article  PubMed  Google Scholar 

  • Patel SK, Mullins WA, O’Neil SH et al (2011) Neuropsychological differences between survivors of supratentorial and infratentorial brain tumours. J Intellect Disabil Res 55(1):30–40

    Article  CAS  PubMed  Google Scholar 

  • Petersen SE, Posner MI (2012) The attention system of the human brain: 20 years after. Annu Rev Neurosci 35:73–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poggi G, Liscio M, Galbiati S et al (2005) Brain tumors in children and adolescents: cognitive and psychological disorders at different ages. Psychooncology 14(5):386–395

    Article  PubMed  Google Scholar 

  • Portteus A, Ahmad N, Tobey D, Leavey P (2006) The prevalence and use of antidepressant medication in pediatric cancer patients. J Child Adolesc Psychopharmacol 16(4):467–473

    Article  PubMed  Google Scholar 

  • Prevatt FF, Heffer RW, Lowe PA (2000) A review of school reintegration programs for children with cancer. J Sch Psychol 38:447–467

    Article  Google Scholar 

  • Pulsifer MB, Sethi RV, Kuhlthau KA et al (2015) Early cognitive outcomes following proton radiation in pediatric patients with brain and central nervous system tumors. Int J Radiat Oncol Biol Phys 93(2):400–407

    Article  PubMed  PubMed Central  Google Scholar 

  • Qiu D, Kwong DL, Chan GC et al (2007) Diffusion tensor magnetic resonance imaging finding of discrepant fractional anisotropy between the frontal and parietal lobes after whole-brain irradiation in childhood medulloblastoma survivors: reflection of regional white matter radiosensitivity? Int J Radiat Oncol Biol Phys 69(3):846–851

    Article  PubMed  Google Scholar 

  • Quillen J, Crawford E, Plummer B et al (2011) Parental follow-through of neuropsychological recommendations for childhood-cancer survivors. J Pediatr Oncol Nurs 28(5):306–310

    Article  PubMed  Google Scholar 

  • Quintero-Gallego EA, Gómez CM, Morales M et al (2011) Spatial orientation deficit in children due to cerebellum astrocytoma pediatric tumor obtained by means of the Attentional Network Test. Neurosci Lett 504(3):232–236

    Article  CAS  PubMed  Google Scholar 

  • Radcliffe J, Bennett D, Kazak AE et al (1996) Adjustment in childhood brain tumor survival: child, mother, and teacher report. J Pediatr Psychol 21(4):529–539

    Article  CAS  PubMed  Google Scholar 

  • Ramanan S, Kooshki M, Zhao W et al (2009) The PPARα agonist, fenofibrate, preserves hippocampal neurogenesis and inhibits microglial activation following whole-brain irradiation. Int J Radiat Oncol Biol Phys 75(3):870–877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rapp SR, Case LD, Peiffer A et al (2015) Donepezil for irradiated brain tumor survivors: a phase iii randomized placebo-controlled clinical trial. J Clin Oncol 33(15):1653–1659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reddick WE, Taghipour DJ, Glass JO et al (2014) Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers. Pediatr Blood Cancer 61(6):1074–1079

    Article  PubMed  PubMed Central  Google Scholar 

  • Riggs L, Bouffet E, Laughlin S et al (2014) Changes to memory structures in children treated for posterior fossa tumors. J Int Neuropsychol Soc 20(02):168–180

    Article  PubMed  Google Scholar 

  • Ris MD, Packer R, Goldwein J et 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

    Article  CAS  PubMed  Google Scholar 

  • Ris MD, Beebe DW, Armstrong FD et al (2008) Cognitive and adaptive outcome in extracerebellar low-grade brain tumors in children: a report from the children’s oncology group. J Clin Oncol 26(29):4765–4770

    Article  PubMed  PubMed Central  Google Scholar 

  • Ris MD, Walsh K, Wallace D et al (2013) Intellectual and academic outcome following two chemotherapy regimens and radiotherapy for average-risk medulloblastoma: COG A9961. Pediatr Blood Cancer 60(8):1350–1357

    Article  PubMed  Google Scholar 

  • Robertson PL, Muraszko KM, Holmes EJ et al (2006) Incidence and severity of postoperative cerebellar Mutism syndrome in children with medulloblastoma: a prospective study by the Children’s Oncology Group. J Neurosurg 105(6 Suppl):444–451

    PubMed  Google Scholar 

  • Robinson KE, Kuttesch JF, Champion JE et al (2010) A quantitative meta-analysis of neurocognitive sequelae in survivors of pediatric brain tumors. Pediatr Blood Cancer 55(3):525–531

    Article  PubMed  Google Scholar 

  • Robinson KE, Wolfe KR, Yeates KO et al (2015) Predictors of adaptive functioning and psychosocial adjustment in children with pediatric brain tumor: a report from the brain radiation investigative study consortium. Pediatr Blood Cancer 62(3):509–516

    Article  PubMed  Google Scholar 

  • Rola R, Raber J, Rizk A et al (2004) Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 188(2):316–330

    Article  CAS  PubMed  Google Scholar 

  • Rynard DW, Chambers A, Klinck AM et al (1998) School support programs for chronically ill children: evaluating the adjustment of children with cancer at school. Child Health Care 27:31–46

    Article  Google Scholar 

  • Sahler OJZ, Varni JW, Fairclough DL et al (2002) Problem-solving skills training for mothers of children with newly diagnosed cancer: a randomized trial. J Dev Behav Pediatr 23(2):77–86

    Article  PubMed  Google Scholar 

  • Sahler OJZ, Phipps S, Mulher RK et 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. J Consult Clin Psychol 73(2):272–283

    Article  PubMed  Google Scholar 

  • Salley CG, Gerhardt CA, Fairclough DL et al (2014) Social self-perception among pediatric brain tumor survivors compared with peers. J Dev Behav Pediatr 35(7):427–434

    Article  PubMed  PubMed Central  Google Scholar 

  • Sands SA, Kellie SJ, Davidow AL et al (2001) Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: from the first international CNS germ-cell tumor study. Neuro-Oncology 3(3):174–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schatz J, Kramer JH, Ablin A et al (2000) Processing speed, working memory, and IQ: a developmental model of cognitive deficits following cranial radiation therapy. Neuropsychology 14(2):189–200

    Article  CAS  PubMed  Google Scholar 

  • Schnegg CI, Greene-Schloesser D, Kooshki M et al (2013) The PPARδ agonist GW0742 inhibits neuroinflammation, but does not restore neurogenesis or prevent early delayed hippocampal-dependent cognitive impairment after whole-brain irradiation. Free Radic Biol Med 61:1–9

    Article  CAS  PubMed  Google Scholar 

  • Schreiber JE, Gurney JG, Palmer SL et al (2014) Examination of risk factors for intellectual and academic outcomes following treatment for pediatric medulloblastoma. Neuro-Oncology 16(8):1129–1136

    Article  PubMed  PubMed Central  Google Scholar 

  • Schulte F, Vannatta K, Barrera M (2014) Social problem solving and social performance after a group social skills intervention for childhood brain tumor survivors. Psychooncology 23(2):183–189

    Article  PubMed  Google Scholar 

  • Shaw EG, Rosdhal R, D’Agostino RB Jr et al (2006) Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life. J Clin Oncol 24(9):1415–1420

    Article  CAS  PubMed  Google Scholar 

  • Silber JH, Radcliffe J, Peckham V et al (1992) Whole brain radiation and decline in intelligence: the influence of dose and age on IQ score. J Clin Oncol 10:1390–1396

    Article  CAS  PubMed  Google Scholar 

  • Spiegler BJ, Bouffet E, Greenberg ML et al (2004) Change in neurocognitive functioning after treatment with cranial radiation in childhood. J Clin Oncol 22(4):706–713

    Article  PubMed  Google Scholar 

  • Thompson SJ, Leigh L, Christensen R et al (2001) Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer. J Clin Oncol 19(6):1802–1808

    Article  CAS  PubMed  Google Scholar 

  • Treiber FA, Schramm L, Mabe PA (1986) Children’s knowledge and concerns towards a peer with cancer: a workshop intervention approach. Child Psychiatry Hum Dev 16:38–44

    Article  Google Scholar 

  • Tsai PF, Yang CC, Chuang CC et al (2015) Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study. Radiat Oncol 10:253–268

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Varni JW, Katz ER, Colegrove R Jr, Dolgin M (1993) The impact of social skills training on the adjustment of children with newly diagnosed cancer. J Pediatr Psychol 18(6):751–767

    Article  CAS  PubMed  Google Scholar 

  • Wiener L, Kazak AE, Noll RB et al (2015) Standards for the psychosocial care of children with cancer and their families: an introduction to the special issue. Pediatr Blood Cancer 62(Suppl 5):S419–S424

    Article  PubMed  Google Scholar 

  • Willard VW, Hardy KK, Allen TM et al (2013) Sluggish cognitive tempo in survivors of pediatric brain tumors. J Neuro-Oncol 114(1):71–78

    Article  Google Scholar 

  • Willard VW, Conklin HM, Boop FA et al (2014) Emotional and behavioral functioning after conformal radiation therapy for pediatric ependymoma. Int J Radiat Oncol Biol Phys 88(4):814–821

    Article  PubMed  PubMed Central  Google Scholar 

  • Willard VW, Conklin HM, Wu S, Merchant TE (2015) Prospective longitudinal evaluation of emotional and behavioral functioning in pediatric patients with low-grade glioma treated with conformal radiation therapy. J Neuro-Oncol 122(1):161–168

    Article  Google Scholar 

  • Winter AL, Conklin HM, Tyc VL et al (2014) Executive function late effects in survivors of pediatric brain tumors and acute lymphoblastic leukemia. J Clin Exp Neuropsychol 36(8):818–830

    Article  PubMed  PubMed Central  Google Scholar 

  • Wolfe KR, Madan-Swain A, Hunter GR et al (2013a) An fMRI investigation of working memory and its relationship with cardiorespiratory fitness in pediatric posterior fossa tumor survivors who received cranial radiation therapy. Pediatr Blood Cancer 60(4):669–675

    Article  PubMed  Google Scholar 

  • Wolfe KR, Walsh KS, Reynolds NC et al (2013b) Executive functions and social skills in survivors of pediatric brain tumor. Child Neuropsychol 19(4):370–384

    Article  PubMed  Google Scholar 

  • Wolfe-Christensen C, Mullins LL, Scott JG, McNall-Knapp RY (2007) Persistent psychosocial problems in children who develop posterior fossa syndrome after medulloblastoma resection. Pediatr Blood Cancer 49(5):723–726

    Article  PubMed  Google Scholar 

  • Wong-Goodrich SJ, Pfau ML, Flores CT et al (2010) Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation. Cancer Res 70(22):9329–9338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang ES, Wang H, Jiang G et al (2009) Lithium-mediated protection of hippocampal cells involves enhancement of DNA-PK-dependent repair in mice. J Clin Invest 119(5):1124–1135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yazlovitskaya EM, Edwards E, Thotala D et al (2006) Lithium treatment prevents neurocognitive deficit resulting from cranial irradiation. Cancer Res 66(23):11179–11186

    Article  CAS  PubMed  Google Scholar 

  • Yeates KO, Bigler ED, Dennis M et al (2007) Social outcomes in childhood brain disorder: a heuristic integration of social neuroscience and developmental psychology. Psychol Bull 133:535–556

    Article  PubMed  PubMed Central  Google Scholar 

  • Yock TI, Tarbell NJ (2004) Technology insight: proton beam radiotherapy for treatment in pediatric brain tumors. Nat Clin Pract Oncol 1:97–103

    PubMed  Google Scholar 

  • Yock TI, Yeap BY, Ebb DH et al (2016) Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study. Lancet Oncol 17(3):287–298

    Article  PubMed  Google Scholar 

  • Zeltzer LK, Recklitis C, Buchbinder D et al (2009) Psychological status in childhood cancer survivors: a report from the childhood cancer survivor study. J Clin Oncol 27(14):2396–2404

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Section of Psychology, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, CC 1630.00, Houston, TX, 77030-2399, USA

    Marsha Nortz Gragert Ph.D. & Tanya N. Antonini Ph.D.

  2. Department of Pediatrics, Section of Psychology, Baylor College of Medicine, Texas Children’s Hospital, 1102 Bates Ave., Suite 940, Houston, TX, 77030-2399, USA

    Lisa S. Kahalley Ph.D.

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  1. Marsha Nortz Gragert Ph.D.
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  2. Tanya N. Antonini Ph.D.
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  3. Lisa S. Kahalley Ph.D.
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Correspondence to Lisa S. Kahalley Ph.D. .

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Editors and Affiliations

  1. Dept. of Radiation Oncology, Mayo Clinic Dept. of Radiation Oncology, Rochester, Minnesota, USA

    Anita Mahajan

  2. MD Anderson Cancer Center, Houston, Texas, USA

    Arnold Paulino

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Gragert, M.N., Antonini, T.N., Kahalley, L.S. (2018). Neuropsychological Late Effects of Radiotherapy for Pediatric Brain Tumors. In: Mahajan, A., Paulino, A. (eds) Radiation Oncology for Pediatric CNS Tumors. Springer, Cham. https://doi.org/10.1007/978-3-319-55430-3_30

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