Neurocognitive function and CNS integrity in adult survivors of childhood hodgkin lymphoma.

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.

• Authors: Kevin R Krull, Noah D Sabin, Wilburn E Reddick, Liang Zhu, Gregory T Armstrong, Daniel M Green, Alejandro R Arevalo, Matthew J Krasin, Deo Kumar Srivastava, Leslie L Robison, Melissa M Hudson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 29 Pg. 3618-24 (Oct 10 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22949149 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines

Topics

• Adolescent
• Adult
• Age Factors
• Anthracyclines (adverse effects, therapeutic use)
• Central Nervous System Diseases (etiology, physiopathology)
• Chemoradiotherapy (adverse effects, methods)
• Child
• Cognition Disorders (epidemiology, etiology, physiopathology)
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Female
• Follow-Up Studies
• Hodgkin Disease (diagnosis, psychology, therapy)
• Humans
• Incidence
• Male
• Middle Aged
• Neuropsychological Tests
• Prospective Studies
• Radiotherapy Dosage
• Risk Assessment
• Sex Factors
• Survivors (psychology)
• Time Factors