Late-onset Cognitive Impairment and Modifiable Risk Factors in Adult Childhood Cancer Survivors

Abstract

ImportanceLong-term survivors of childhood cancer may be at elevated risk for new neurocognitive impairment and decline as they age into adulthood.ObjectiveTo determine whether aging adult childhood cancer survivors report more new-onset neurocognitive impairments compared with their siblings and to identify risk factors associated with such impairments.Design, Setting, and ParticipantsParticipants of this cohort study included adult survivors of childhood cancer from the Childhood Cancer Survivor Study and their siblings as a control group. The original cohort included survivors who received a diagnosis between January 1, 1970, and December 31, 1986, for whom longitudinal neurocognitive assessment was available. This study examined the prevalence of new-onset neurocognitive impairment between baseline (23.4 years after diagnosis) and follow-up (35.0 years after diagnosis). The analysis was performed from January 2021 to May 2022.ExposuresCancer treatment exposures were abstracted from medical records. Chronic health conditions were graded using Common Terminology Criteria for Adverse Events version 4.03.Main Outcomes and MeasuresThe primary outcome was new-onset (present at follow-up, but not present at baseline) neurocognitive impairment (defined as a score in the worst 10% of the sibling cohort). Impairment was assessed using the Childhood Cancer Survivor Study Neurocognitive questionnaire. Relative risks (RRs) and 95% CIs were used to estimate associations of neurocognitive impairment with treatment and health behaviors and conditions using generalized linear models.ResultsThe cohort comprised 2375 survivors (mean [SD] age at evaluation, 31.8 [7.5] years; 1298 women [54.6%]) of childhood cancer, including acute lymphoblastic leukemia (ALL; 1316 participants), central nervous system (CNS) tumors (488 participants), and Hodgkin lymphoma (HL; 571 participants). A total of 232 siblings (mean [SD] age at evaluation, 34.2 [8.4] years; 134 women [57.8%]) were included. Compared with siblings, a higher proportion of survivors with no impairment in memory at baseline had new-onset memory impairment at follow-up: siblings proportion, 7.8% (95% CI, 4.3%-11.4%); ALL survivors treated with chemotherapy only, 14.0% (95% CI, 10.7%-17.4%); ALL survivors treated with cranial radiation (CRT), 25.8% (95% CI, 22.6%-29.0%); CNS tumor survivors, 34.7% (95% CI, 30.0%-39.5%); and HL survivors, 16.6% (95% CI, 13.4%-19.8%). New-onset memory impairment was associated with CRT in CNS tumor survivors (RR, 1.97; 95% CI, 1.33-2.90) and alkylator chemotherapy greater than or equal to 8000 mg/m2 in ALL survivors treated without CRT (RR, 2.80; 95% CI, 1.28-6.12). Neurologic conditions mediated the impact of CRT on new-onset memory impairment in CNS survivors. Smoking, low educational attainment, and low physical activity were associated with elevated risk for new-onset memory impairment.Conclusions and RelevanceThese findings suggest that adult survivors of childhood cancer are at elevated risk for late-onset memory impairment related to modifiable risk factors identified early in survivorship.

Burden of Childhood Cancer and the Social and Economic Challenges in Adulthood

“…Poor outcomes of CNS survivors can be attributed to the significant impact of the nature of their disease and its treatment on cognitive performance. 248 Our findings suggest that CCSs have similar rates of employment when all cancer survivors are taken into consideration; however, a comparison of siblings showed significantly worse rates of employment, similar to education. Subgroup analysis showed that survivors of hematological malignancies, solid tumors, and those who underwent HSCT as part of their treatment were all more likely to be unem-ployed, with CNS survivors having the worst rates, being almost 3 times more likely to be unemployed.…”

“…These results are consistent with prior research by Schulte et al and partially align with the results of Saatci et al Sibling comparisons underscore educational difficulties of CCSs amid similar family background and socioeconomic status. Poor outcomes of CNS survivors can be attributed to the significant impact of the nature of their disease and its treatment on cognitive performance …”