Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA.
School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
Ann Neurol. 2021 Mar;89(3):534-545. doi: 10.1002/ana.25981. Epub 2020 Dec 31.
This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs).
Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age-adjusted z score < 10th percentile. Participants impaired on ≥3 tests had global impairment. CHCs were graded using the Common Terminology Criteria for Adverse Events v4.3 (grade 1, mild; 2, moderate; 3, severe/disabling; 4, life-threatening) and were combined into a severity/burden score by frequency and grade (none/low, medium, high, and very high). A total of 1,598 survivors received CNS-directed therapy including cranial radiation, intrathecal methotrexate, or neurosurgery. Logistic regression estimated the odds of neurocognitive impairment associated with severity/burden score and grade 2 to 4 conditions, stratified by CNS treatment.
CNS-treated survivors performed worse than non-CNS-treated survivors on all neurocognitive tests and were more likely to have global neurocognitive impairment (46.9% vs 35.3%, p < 0.001). After adjusting for demographic and treatment factors, there was a dose-response association between severity/burden score and global neurocognitive impairment, but only among CNS-treated survivors (high odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1.42-3.53; very high OR = 4.07, 95% CI = 2.30-7.17). Cardiovascular and pulmonary conditions were associated with processing speed, executive function, and memory impairments in CNS-treated but not non-CNS-treated survivors who were impacted by neurologic conditions.
Reduced cognitive/brain reserve associated with CNS-directed therapy during childhood may make survivors vulnerable to adverse cognitive effects of cardiopulmonary conditions during adulthood. ANN NEUROL 2021;89:534-545.
本研究以儿童癌症幸存者为新型模型，旨在探讨中枢神经系统（CNS）损伤患儿是否存在发生与后续迟发性慢性健康状况（CHC）相关的神经认知障碍的风险更高。
接受过儿童癌症治疗的成年幸存者（n=2859，诊断后≥10 年，≥18 岁）完成了全面的神经认知测试和临床检查。采用年龄校正 z 评分＜第 10 百分位数定义为神经认知障碍。≥3 项测试受损的患者存在整体障碍。采用通用不良事件术语标准 4.3（grade 1，轻度；2，中度；3，重度/致残；4，危及生命）对 CHC 进行分级，并根据频率和级别（无/低、中、高、极高）将其组合成严重程度/负担评分。共有 1598 名幸存者接受了包括颅部放疗、鞘内甲氨蝶呤或神经外科手术在内的 CNS 定向治疗。采用 logistic 回归估计严重程度/负担评分和 2 至 4 级疾病与神经认知障碍的关联的比值比（OR），并根据 CNS 治疗进行分层。
与未接受 CNS 治疗的幸存者相比，接受 CNS 治疗的幸存者在所有神经认知测试中表现更差，且更有可能出现整体神经认知障碍（46.9% vs 35.3%，p<0.001）。在校正人口统计学和治疗因素后，严重程度/负担评分与整体神经认知障碍之间存在剂量反应关系，但仅在接受 CNS 治疗的幸存者中存在（高 OR=2.24，95%置信区间 [CI]：1.42-3.53；极高 OR=4.07，95% CI：2.30-7.17）。心血管和肺部疾病与接受 CNS 治疗的幸存者的处理速度、执行功能和记忆障碍相关，但与未接受 CNS 治疗的受神经疾病影响的幸存者无关。
儿童时期接受 CNS 定向治疗导致的认知/大脑储备减少，可能使幸存者在成年后易受心肺疾病不良认知影响。ANN NEUROL 2021；89：534-545。
