Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes

Abstract

Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18-47 years]; median time since diagnosis, 15.5 years [range, 6.5-42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.

Fig. 1.

Timing of assessments relative to time since diagnosis. Each line represents an individual participant identified as a number on the y-axis; the number of points on the line represents the number of assessments conducted for that participant. Yrs, years.

Fig. 2.

Mean z-scores for medulloblastoma survivors across 8 neurocognitive domains. Error bars are standard deviations (SDs). Shaded area represents the average range based on population norms (mean = 0, SD = 1). Z-transformed intelligence quotient (IQ) scores equivalent to mean scaled scores of 87.1 ± 13.1, 90.2 ± 16.4, and 81.9 ± 15.2 for verbal comprehension, perceptual organization, and working memory, respectively, based on population mean of 100 ± 15. *Statistically significant difference between survivors and population norms.

Fig. 3.

Change in working memory (A) and level of impairment (B) as a function of time since diagnosis. Shaded area represents the average range. Age at diagnosis groupings provided for illustrative purposes. Solid lines are individual patient scores joined together; the dotted line represents the linear trend. X: diagnosed at age <5 years; O: diagnosed between the ages of 5–7.9 years; □: diagnosed at the age ≥8 years.