Neurocognitive and psychosocial outcomes in adult survivors of childhood soft-tissue sarcoma: A report from the St. Jude Lifetime Cohort

Background: To the authors' knowledge, few studies to date have examined long-term neurocognitive outcomes in survivors of childhood soft-tissue sarcoma. Methods: A total of 150 survivors (41% of whom were female with a mean current age of 33 years [SD, 8.9 years] and a time since diagnosis of 24 years [SD, 8.7 years]) and 349 community controls (56% of whom were female with a mean current age of 35 years [SD, 10.2 years]) completed comprehensive neuropsychological testing, echocardiography, electrocardiography, pulmonary function tests, endocrine evaluation, and physical examination. Patient-reported outcomes of health-related quality of life (HRQOL) and social attainment were collected. Survivors were compared with norms and controls on neurocognitive outcomes using general linear models, and on HRQOL and social attainment using modified Poisson models. The impacts of treatment and chronic health conditions on outcomes were examined using multivariable general linear models (effect size was expressed as unstandardized β estimates that reflected the unit of change from a mean of 0 and an SD of 1) and modified Poisson models (effect size expressed as relative risks). Results: Compared with controls and population norms, survivors demonstrated lower performance on measures of verbal reasoning (mean z score, −0.45 [SD, 1.15]; P <.001) mathematics (mean z score, −0.63 [SD, 1.07]; P <.001), and long-term memory (mean z score, −0.37 [SD, 1.14]; P <.001). Cumulative anthracycline exposure (per 100 mg/m²) was found to be associated with poorer verbal reasoning (β = −0.14 z scores; P =.04), reading (β = −0.09 z score; P =.04), and patient-reported vitality (relative risk, 1.32; 95% CI, 1.09-1.59). Neurologic and neurosensory chronic conditions were associated with poorer mathematics (neurologic conditions: β = −0.63 z score [P = 0.02]; and hearing impairment: β = −0.75 z scores [P < 0.01]). Better cognitive performance was associated with higher social attainment. Conclusions: Long-term survivors of soft-tissue sarcoma are at risk of neurocognitive problems and poor HRQOL associated with anthracycline treatment and chronic health conditions.