Neurocognitive function and CNS integrity in adult survivors of childhood Hodgkin lymphoma

Kevin R. Krull, Noah D. Sabin, Wilburn E. Reddick, Liang Zhu, Gregory Armstrong, Daniel M. Green, Alejandro R. Arevalo, Matthew J. Krasin, Deo Kumar Srivastava, Leslie L. Robison, Melissa M. Hudson

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Abstract

Purpose: Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL. Patients and Methods: In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations. Results: Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E′; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E′]; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [ DL co corr; P = .04), and leukoencephalopathy ( P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency ( P = .001). Working memory impairment was associated with E/E′, although impaired sustained attention and naming speed were associated with DL co corr. Neurocognitive performance was associated with academic and vocational functioning. Conclusion: These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.

Original languageEnglish (US)
Pages (from-to)3618-3624
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number29
DOIs
StatePublished - Oct 10 2012

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Hodgkin Disease
Survivors
Leukoencephalopathies
Short-Term Memory
Radiation Dosage
Thorax
Pulmonary Diffusing Capacity
Magnetic Resonance Imaging
Long-Term Memory
Anthracyclines
Respiratory Function Tests
Brain
Carbon Monoxide
Neuroimaging
Physical Examination
Stroke
Radiation
Lung
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Krull, K. R., Sabin, N. D., Reddick, W. E., Zhu, L., Armstrong, G., Green, D. M., ... Hudson, M. M. (2012). Neurocognitive function and CNS integrity in adult survivors of childhood Hodgkin lymphoma. Journal of Clinical Oncology, 30(29), 3618-3624. https://doi.org/10.1200/JCO.2012.42.6841

Neurocognitive function and CNS integrity in adult survivors of childhood Hodgkin lymphoma. / Krull, Kevin R.; Sabin, Noah D.; Reddick, Wilburn E.; Zhu, Liang; Armstrong, Gregory; Green, Daniel M.; Arevalo, Alejandro R.; Krasin, Matthew J.; Srivastava, Deo Kumar; Robison, Leslie L.; Hudson, Melissa M.

In: Journal of Clinical Oncology, Vol. 30, No. 29, 10.10.2012, p. 3618-3624.

Research output: Contribution to journalArticle

Krull, KR, Sabin, ND, Reddick, WE, Zhu, L, Armstrong, G, Green, DM, Arevalo, AR, Krasin, MJ, Srivastava, DK, Robison, LL & Hudson, MM 2012, 'Neurocognitive function and CNS integrity in adult survivors of childhood Hodgkin lymphoma', Journal of Clinical Oncology, vol. 30, no. 29, pp. 3618-3624. https://doi.org/10.1200/JCO.2012.42.6841
Krull, Kevin R. ; Sabin, Noah D. ; Reddick, Wilburn E. ; Zhu, Liang ; Armstrong, Gregory ; Green, Daniel M. ; Arevalo, Alejandro R. ; Krasin, Matthew J. ; Srivastava, Deo Kumar ; Robison, Leslie L. ; Hudson, Melissa M. / Neurocognitive function and CNS integrity in adult survivors of childhood Hodgkin lymphoma. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 29. pp. 3618-3624.
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abstract = "Purpose: Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL. Patients and Methods: In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations. Results: Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53{\%} of survivors, and 37{\%} had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E′; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E′]; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [ DL co corr; P = .04), and leukoencephalopathy ( P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency ( P = .001). Working memory impairment was associated with E/E′, although impaired sustained attention and naming speed were associated with DL co corr. Neurocognitive performance was associated with academic and vocational functioning. Conclusion: These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.",
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AU - Sabin, Noah D.

AU - Reddick, Wilburn E.

AU - Zhu, Liang

AU - Armstrong, Gregory

AU - Green, Daniel M.

AU - Arevalo, Alejandro R.

AU - Krasin, Matthew J.

AU - Srivastava, Deo Kumar

AU - Robison, Leslie L.

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N2 - Purpose: Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL. Patients and Methods: In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations. Results: Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E′; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E′]; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [ DL co corr; P = .04), and leukoencephalopathy ( P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency ( P = .001). Working memory impairment was associated with E/E′, although impaired sustained attention and naming speed were associated with DL co corr. Neurocognitive performance was associated with academic and vocational functioning. Conclusion: These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.

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