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Cited by 121Childhood Cancer Survivors' Quality of LifeCancer-related cognitive impairment studiesAcute Lymphoblastic Leukemia research

Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers

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Reddick, Wilburn E., Taghipour, Delaram J., Glass, John O., Ashford, Jason, Xiong, Xiaoping, Wu, Shengjie, Bonner, Melanie, Khan, Raja B. +1 more·2014·Pediatric Blood & Cancer
DOI 10.1002/pbc.24947PMC PMC4053257
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Abstract

Objective: In children, CNS‐directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls. Procedures: The effects of host characteristics and CNS treatment intensity on WMV were investigated in 383 childhood cancer survivors (199 ALL, 184 BT) at least 12 months post‐completion of therapy and 67 healthy siblings that served as a control group. t‐Tests and multiple variable linear models were used to assess cross‐sectional WMV and its relation with neurocognitive function. Results: BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a larger impact on estimated IQ among females and children treated at a younger age. Conclusions: Survivors of childhood cancer that have undergone higher intensity therapy at a younger age have significantly less WMV than their peers and this difference increases with time since therapy. Decreased WMV is associated with significantly lower scores in intelligence, attention, and academic performance in survivors. Pediatr Blood Cancer 2014;61:1074–1079. © 2014 Wiley Periodicals, Inc.

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  • Reductions in total white matter volume and increased fractional anisotropy have been reported in adult survivors of childhood ALL.

    “Reductions in total white matter volume and increased fractional anisotropy have been reported in adult survivors of childhood ALL (Aukema et al., 2009; Edelmann et al., 2014; Reddick et al., 2014),”

    From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Reddick et al., 2014

    The Results (Volumetric Assessment) report reduced white matter volume in cancer survivors, including those treated for ALL. But the Methods (Patients) specify participants aged 6–18, and the Discussion says this study did not measure fractional anisotropy; it reports that other studies found decreased, not increased, fractional anisotropy. Its volume assessment was also limited to a specific anatomical area, rather than the whole brain. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Females may be at greater risk for cognitive late effects after cancer treatment.

    “On the other hand, females may be at greater risk for cognitive late effects after cancer treatment (Buizer, de Sonneville, & Veerman, 2009; Hudson et al., 2003; Reddick et al., 2014; Waber, Tarbell, Kahn, Gelber, & Sallan, 1992).”

    From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Reddick et al., 2014

    The Results (Neurocognitive Performance; page unavailable) report that, at comparable white matter volumes, female childhood cancer survivors with smaller volumes had lower IQs than males. This supports a possible female vulnerability, but the finding concerns IQ in relation to white matter volume; it does not establish a greater risk for cognitive late effects generally after cancer treatment. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • There is some evidence of associations between white matter morphology and measures of attention and intelligence in survivors of childhood ALL.

    “with some evidence of associations between white matter morphology and measures of attention and intelligence (Edelmann et al., 2014; Reddick et al., 2014) and motor processing speed (Aukema et al., 2009).”

    From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Reddick et al., 2014

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References 43 · Cited by 121

Research works printed but not linked: 39

  1. [1]Pui C-H Sandlund JT Pei D Improved outcome for children with acute lymphoblastic leukemia: results of total therapy study XIIIB at St Jude Children’s Research Hopital Blood 2004 104 2690 2696 15251979
  2. [2]Pui C-H Campana D Pei D Treating childhood acute lymphoblastic leukemia without cranial irradiation N Engl J Med 2009 360 2730 2741 19553647 PMC2754320
  3. [3]CBTRUS CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004-2008 2012 PMC4623240 26511214
  4. [4]Packer RJ Gajjar A Vezina G Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma J Clin Oncol 2006 24 4202 4208 16943538
  5. [5]Gajjar A Chintagumpala M Ashley D Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial Lancet Oncol 2006 7 813 820 17012043
  6. [6]Oeffinger KC Mertens AC Sklar CA Chronic health conditions in adult survivors of childhood cancer N Engl J Med 2006 355 1572 1582 17035650
  7. [7]Pui C-H Pei D Sandlund JT Risk of adverse events after completion of therapy for childhood acute lymphoblastic leukemia J Clin Oncol 2005 23 7936 7941 16258093
  8. [8]Spiegler BJ Kennedy K Maze R Comparison of long-term neurocognitive outcomes in young children with acute lymphoblastic leukemia treated with cranial radiation or high-dose or very high-dose intravenous methotrexate J Clin Oncol 2006 24 3858 3864 16921038
  9. [9]Campbell LK Scaduto M Sharp W A meta-analysis of the neurocognitve sequelae of treatment for childhood acute lymphocytic leukemia Pediatr Blood Cancer 2007 49 65 73 16628558
  10. [10]Mulhern RK Merchant TE Gajjar A Late neurocognitive sequelae in survivors of brain tumors in childhood Lancet 2004 5 399 408 15231246
  11. [11]Buizer AI De Sonneville LMJ van den Heuvel-Eibrink MM Veerman AJP Chemotherapy and attentional dysfunction in survivors of childhood acute lymphoblastic leukemia: effect of treatment intensity Pediatr Blood Cancer 2005 45 281 290 15806539
  12. [12]Mulhern RK Palmer SL Merchant TE Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma J Clin Oncol 2005 23 5511 5519 16110011
  13. [13]Mabbott DJ Penkman L Witol A Core neurocognitive functions in children treated for posterior fossa tumors Neuropsychology 2008 22 159 168 18331158
  14. [14]Jain N Krull KR Brouwers P Neuropsychological outcome following intensity-modulated radiation therapy for pediatric medulloblastoma Pediatr Blood Cancer 2008 51 275 279 18421716
  15. [15]Reeves CB Palmer SL Reddick WE Attention and memory functioning among pediatric patients with medulloblastoma J Pediatr Psychol 2006 31 272 280 15788715
  16. [16]Ashford J Schoffstall C Reddick WE Attention and working memory abilities in children treated for acute lymphoblastic leukemia Cancer 2010 116 4638 4645 20572038 PMC2946517
  17. [17]Mabbott DJ Monsalves E Spiegler BJ Longitudinal evaluation of neurocognitive function after treatment for central nervous system germ cell tumors in childhood Cancer 2011 117 5402 5411 21563173
  18. [18]Mulhern RK Butler RW Neurocognitive sequelae of childhood cancers and their treatment Pediatr Rehabil 2004 7 1 14 14744668
  19. [19]Filley CM Kleinschmidt-DeMasters BK Toxic leukoencephalopathy N Engl J Med 2001 345 425 432 11496854
  20. [20]Mulhern RK Reddick WE Palmer SL Neurocognitive deficits in medulloblastoma survivors and white matter loss Ann Neurol 1999 46 834 841 10589535
  21. [21]Reddick WE Russell JM Glass JO Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced-dose cranial-spinal irradiation Magn Reson Imaging 2000 18 787 793 11027871
  22. [22]Mulhern RK Palmer SL Reddick WE Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss J Clin Oncol 2001 19 472 479 11208841
  23. [23]Reddick WE Glass JO Palmer SL Atypical white matter volume development in children following craniospinal irradiation Neuro Onc 2005 7 12 19 PMC1871625 15701278
  24. [24]Reddick WE Glass JO Helton KJ Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate AJNR Am J Neuroradiol 2005 26 1263 1269 15891195 PMC2396789
  25. [25]Reddick WE Glass JO Helton KJ A quantitative MRI assessment of leukoencephalopathy in children treated for acute lymphoblastic leukemia without irradiation AJNR Am J Neuroradiol 2005 26 2371 2377 16219848 PMC2396879
  26. [26]Paakko E Harila-Saari A Vanionpaa L White matter changes on MRI during treatment in children with acute lymphoblastic leukemia: correlation with neuropsychological findings Med Pediatr Oncol 2000 35 456 461 11070477
  27. [27]Chu WCW Chik KW Chan YL White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia: longitudinal study with MR imaging and 1H MR spectroscopy Radiology 2003 229 659 669 14576448
  28. [28]Mulhern RK Khan RB Kaplan S Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer J Clin Oncol 2004 22 4795 4803 15570081
  29. [34]Blatter DD Bigler ED Gale SD Quantitative volumetric analysis of brain MR: normative database spanning 5 decades of life AJNR Am J Neuroradiol 1995 16 241 251 7726068 PMC8338340
  30. [35]Matsumae M Kikinis R Morocz I Age-related changes in intracranial compartment volumes in normal adults assessed by magnetic resonance imaging J Neurosurg 1996 84 982 991 8847593
  31. [36]Glass JO Ji Q Glas LS Reddick WE Prediction of total cerebral tissue volumes in normal appearing brain from subsampled segmentation volumes Magn Reson Imaging 2003 21 977 982 14684199
  32. [37]Ji Q Glass JO Reddick WE A novel, fast entropy-minimization algorithm for bias field correction in MR images Magn Reson Imaging 2007 25 259 264 17275623 PMC2394719
  33. [38]Reddick WE Glass JO Cook EN Automated segmentation and classification of multispectral magnetic resonance images of brain using artifical neural networks IEEE Trans Med Imaging 1997 16 911 918 9533591
  34. [39]Connor JR Menzies SL Relationship of iron to oligodendrocytes and myelination Glia 1996 17 83 93 8776576
  35. [40]Vymazal J Brooks RA Baumgarner C The relation between brain iron and NMR relaxation times: an in vitro study Magn Reson Med 1996 35 56 61 8771022
  36. [41]Smith B Brain damage after intrathecal methotrexate J Neurol Neurosurg Psychiatry 1975 38 810 815 1058923 PMC492077
  37. [42]Mabbott DJ Noseworthy M Bouffet E Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ Neuro Onc 2006 8 244 252 PMC1871945 16723629
  38. [43]Aukema EJ Caan MWA Oudhuis N White matter fractional anisotropy correlates with speed of processing and motor speed in young childhood cancer survivors Int J Radiat Oncol Biol Phys 2009 74 837 843 19117694
  39. [44]Palmer SL Glass JO Li Y White matter integrity is associated with cognitive processing in patients treated for a posterior fossa brain tumor Neuro Oncol 2012 14 1185 1193 22898373 PMC3424215

Authors
Reddick, W. E., Taghipour, D. J., Glass, J. O., Ashford, J., Xiong, X., Wu, S., Bonner, M., Khan, R. B., & Conklin, H. M.
Affiliations
  • St. Jude Children's Research Hospital (US)
  • Duke University (US)
Corresponding author
Reddick, Wilburn E.
ORCID
Venue
Pediatric Blood & Cancer
Publisher
Wiley
Published
2014-01-25
Volume
61
Issue
6
Pages
1074-1079
ISSN
  • 1545-5009 (ISSN-L)
  • 1545-5017
DOI
10.1002/pbc.24947
PMC
PMC4053257
OpenAlex
W1581481118
Cited by
121
References
43
Citations by year
2026: 4 · 2025: 8 · 2024: 16 · 2023: 8 · 2022: 13 · 2021: 12 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 10 · 2016: 7 · 2015: 11 · 2014: 5
FWCI
10.35
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Pediatric Blood & Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (P30 CA21765, R01 CA078957, R01 CA90246, U01 CA81445)
  • American Lebanese Syrian Associated Charities
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
Keywords
childhood cancer survivors, white matter volume, neurocognitive impairment, acute lymphoblastic leukemia, malignant brain tumors, prognostic factors, attention, academic performance, intelligence, age at treatment, time since treatment, sex differences
MeSH terms
Age Factors, Antineoplastic Agents, Attention, Attention Deficit Disorder with Hyperactivity, Brain, Brain Damage, Chronic, Brain Neoplasms, Child, Child, Preschool, Cross-Sectional Studies, Educational Status, Female, Follow-Up Studies, Humans, Injections, Spinal, Intelligence, Learning Disabilities, Magnetic Resonance Imaging, Male, Methylphenidate, Neuropsychological Tests, Organ Size, Prognosis, Prospective Studies, Radiation Injuries, Risk, Cranial Irradiation, Survivors, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukoencephalopathies

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