Departments of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN.
Psychology and Biostatistics, St. Jude Children's Research Hospital, Memphis, TN.
J Natl Cancer Inst. 2018 Apr 1;110(4):411-419. doi: 10.1093/jnci/djx224.
Neurocognitive impairment in survivors of childhood cancer may be associated with direct neurotoxicity, as well as indirect effects of systemic health complications. We evaluated associations among treatment exposures, chronic health conditions, and neurocognitive outcomes in adult survivors of childhood cancer.
Participants included 5507 adult survivors of childhood cancer (47.1% male; mean [SD] age = 31.8 [7.6] years at evaluation; 23.1 [4.5] years postdiagnosis) in the Childhood Cancer Survivor Study who completed a self-report measure of neurocognitive function. Cardiac, pulmonary, and endocrine chronic health conditions were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Structural equation modeling was used to examine a priori hypothesized causal pathways among cancer treatment, subsequent chronic health conditions, and neurocognitive outcomes. Multivariable models were used to estimate relative risk for associations of treatments and chronic conditions on neurocognitive function. All statistical tests were two-sided.
One-third of survivors with a grade 2 or higher chronic condition reported impairments in task efficiency and memory. In addition to direct effects of cranial radiation, path analyses and multivariable models demonstrated direct effects of cardiopulmonary (β = 0.10, P = .002; relative risk [RR] = 1.27, 95% confidence interval [CI] = 1.12 to 1.44) and endocrine (β = 0.07, P = .04; RR = 1.14, 95% CI = 1.02 to 1.28) conditions on impaired task efficiency. We identified similar effects of cardiopulmonary condition on memory (P = .01) and emotional regulation (P = .01). Thoracic radiation was associated with impaired task efficiency (P = .01) and emotional regulation (P = .01) through endocrine morbidity.
Non-neurotoxic exposures, such as thoracic radiation, can adversely impact survivors' neurocognitive function through chronic conditions. Management of chronic diseases may mitigate neurocognitive outcomes among aging survivors of childhood cancer.
儿童癌症幸存者的神经认知障碍可能与直接的神经毒性以及全身健康并发症的间接影响有关。我们评估了儿童癌症幸存者的治疗暴露、慢性健康状况与神经认知结局之间的关联。
参与者包括来自儿童癌症幸存者研究的 5507 名成年儿童癌症幸存者（47.1%为男性；评估时的平均[标准差]年龄为 31.8[7.6]岁；诊断后 23.1[4.5]岁），他们完成了一项神经认知功能的自我报告测量。使用国家癌症研究所不良事件通用术语标准（版本 4.03）对心脏、肺部和内分泌慢性健康状况进行分级。结构方程模型用于检验癌症治疗、随后的慢性健康状况与神经认知结局之间预先假设的因果途径。多变量模型用于估计治疗和慢性疾病与神经认知功能之间关联的相对风险。所有统计检验均为双侧检验。
三分之一患有 2 级或更高级别慢性疾病的幸存者报告在任务效率和记忆方面存在障碍。除了颅放射治疗的直接影响外，路径分析和多变量模型还显示了心肺（β=0.10，P=0.002；相对风险[RR]=1.27，95%置信区间[CI]：1.12 至 1.44）和内分泌（β=0.07，P=0.04；RR=1.14，95% CI：1.02 至 1.28）疾病对任务效率受损的直接影响。我们发现心肺疾病对记忆（P=0.01）和情绪调节（P=0.01）也有类似的影响。胸部放射治疗通过内分泌发病率与任务效率受损（P=0.01）和情绪调节受损（P=0.01）有关。
非神经毒性暴露，如胸部放射治疗，可通过慢性疾病对儿童癌症幸存者的神经认知功能产生不利影响。慢性疾病的管理可能会减轻儿童癌症幸存者衰老时的神经认知结局。
