A “new finding” that long-term survivors of childhood Hodgkin lymphoma may be at risk for neurocognitive impairment and central nervous system (CNS) pathology arose from a study among 62 patients treated with either high-dose (≥ 30 Gy) thoracic radiation or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline therapy.
“Compared with national age-adjusted norms, [Hodgkin lymphoma] 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),” the researchers reported in the Journal of Clinical Oncology. Previous research had shown that Hodgkin lymphoma survivors treated with radiation were at risk for cardiac and pulmonary morbidity related to dose of mantle-field radiation exposure.
Patients were randomly selected from a cohort of more than 400 adult survivors of childhood Hodgkin lymphoma in the St. Jude Lifetime Cohort Study. Mean age of the study participants was 42.2 years, and the mean age at diagnosis was 15.1 years. As part of the study, the patients had neurocognitive evaluations, brain MRI, echocardiograms, pulmonary function tests, and physical examinations.
“Survivors demonstrated high rates of neuropathology on structural brain imaging, with leukoencephalopathy identified in 53% of survivors,” the investigators noted. “CNS pathology was associated with neurocognitive impairment.”
Compared to survivors of CNS tumors and acute lymphoblastic leukemia, Hodgkin lymphoma survivors are more likely to experience neurocognitive impairment at a later stage of development, “a factor that will reduce the impact on core academic skills because most survivors will have completed their primary and secondary education before the delayed onset of cardiac and pulmonary morbidity. Thus, neurocognitive impairment in [Hodgkin lymphoma] is likely to have a negative impact during postsecondary education and employment, as was demonstrated in this study. This pattern may account for the fact that the neurocognitive deficits in long-term survivors of [Hodgkin lymphoma] have gone unreported before this study.”
The authors noted that “given the delayed onset, preventive interventions should be considered. Primary prevention has begun with the transition from mantle-field radiation to modern protocols that incorporate combined-modality therapy with reduced dose, limited-volume radiation, and polychemotherapy (eg, anthracyclines and bleomycin). Although this approach may reduce long-term morbidity, significant risk is likely to remain, given the known associations between anthracyclines and cardiac toxicity and bleomycin and pulmonary toxicity. Longitudinal follow-up of such cohorts will be important to fully evaluate long-term neurocognitive and CNS pathology outcomes.” ■
Krull KR, et al: J Clin Oncol. September 4, 2012 (early release online).