Central Nervous System Integrity in Adult Survivors of Childhood Hodgkin Lymphoma,

Abstract 3647

Long-term survivors of childhood Hodgkin Lymphoma (HL) are at risk for cardiopulmonary complications. Although HL survivors are generally not exposed to treatments directed at the central nervous system (CNS), cardiac and pulmonary abnormalities are associated with CNS dysfunction in non-cancer populations. The aim of the current study was to examine neurocognitive and neuroanatomical outcomes in adult survivors of childhood HL.

62 adult survivors (current age mean=43.2, SD=4.79, range=34.4–55.6 years; age at diagnosis mean=15.1, SD=3.31, range=5.85–19.00 years) were identified by stratified random selection from a large cohort treated with either high dose (≥ 30 Gy) thoracic radiation (n=38) or lower dose (< 30Gy) thoracic radiation combined with anthracycline (n=24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical exams. MRI techniques included T1 and T2 weighted imaging, as well as susceptibility weighted imaging (SWI). Images were objectively processed to obtain global diffusion tensor imaging (DTI) and regional cortical thickness. Images were also reviewed and systematically coded by a board certified neuroradiologist.

Compared to national age-adjusted norms, HL survivors demonstrated lower performance on attention span (p=0.01), sustained attention (p=0.01), short-term memory (p=0.001), long-term memory (p=0.006), motor dexterity (p<0.001), and cognitive fluency (p=0.007). Brain MRI revealed some degree of white matter disease (e.g. leukoencephalopathy) in 51.8% of survivors, 68.5% had at least mild cerebral atrophy, and 30.0% had SWI suggestive of cerebrovascular abnormalities. Survivors with evidence of cerebrovascular abnormalities on SWI demonstrated cortical thinning in dorsolateral frontal regions (p=0.006), those with cerebral atrophy had DTI evidence of reduced white matter integrity (p=0.04). Increased attention problems were correlated with decreased cortical thickness in frontal brain regions (p=0.03), while survivors with leukoencephalopathy demonstrated reduced cognitive fluency (p=0.001). Neurocognitive and neuroanatomical measures were associated with abnormal cardiac and pulmonary test results. Focused attention was decreased in patients with lower pulmonary forced expiratory flow (FEF; p=0.04), lower hemoglobin (p=0.02), and lower left ventricular ejection fraction (p=0.04). Long-term memory was decreased in patients with lower hemoglobin (p=0.008), and higher diastolic blood pressure (p=0.02). Survivors with SWI evidence of cerebrovascular abnormalities demonstrated reduced pulmonary FEF (p=0.03). Neurocognitive impairment was associated with dose of thoracic radiation.

These results suggest that adult long-term survivors of HL are at increased risk for neurocognitive impairment, which is associated with radiological indices suggestive of reduced brain integrity and occurs in the presence of symptoms of cardiopulmonary dysfunction.