Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes
Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes
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DOI：
10.1001/jamaneurol.2018.0963
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发表时间：
2018-08-01
期刊：
影响因子：
29
通讯作者：
Park, Susanna B.
中科院分区：
文献类型：
--
作者：
Kandula, Tejaswi;Farrar, Michelle Anne;Park, Susanna B.
重要性 鉴于儿童癌症患者的良好长期生存率，有必要筛查影响长期幸存者健康、功能和生活质量的因素。 目的 全面评估儿童癌症幸存者化疗引起的周围神经病变，以确定疾病负担和功能影响，并提供筛查建议。 设计、环境和参与者 在这项横断面观察性研究中，研究对象为 17 岁之前因颅外恶性肿瘤接受化疗的癌症幸存者2015 年 4 月至 2016 年 12 月期间，从一家三级医院的综合癌症生存诊所连续招募受试者，并与年龄匹配的健康对照组进行比较。研究人员对化疗的类型一无所知。共有 169 名患者符合纳入标准，其中 48 名 (28.4%) 无法联系或拒绝参与。暴露已知对周围神经有毒的化疗药物。主要结果和测量在不同神经毒性化疗药物的接受者和对照参与者之间使用总神经病变评分进行临床周围神经学评估，并与神经生理学、功能和患者报告的结果测量相关，121 例患者的结果本研究纳入的儿童癌症幸存者中，65 名（53.7%）为男性，该队列在中位（范围）年龄 16（7-47）岁、治疗完成后中位（范围）8.5（1.5-29）岁进行神经毒性评估，长春花生物碱和铂化合物是主要的神经毒性药物。与周围神经病变一致的临床异常很常见，在接受神经毒性化疗的 100 名参与者中，有 53 名 (53.0%) 出现（平均总神经病变评分增加，2.1；95% CI，1.4-2.9；P < 0.001），并且与下肢主要感觉轴突神经病变相关（平均振幅降低，5.8 mu V；95% CI， 2.8-8.8；P<0.001)。功能缺陷表现为手动灵活性、远端感觉和平衡。患者报告的结果表明整体生活质量和身体功能的下降与总神经病变评分相关。顺铂比长春花生物碱更频繁地产生长期神经毒性。结论和相关性由周围神经病变引起的临床异常在儿童癌症幸存者中很常见，并且长期持续存在，同时患者报告的结果存在缺陷。在筛查幸存者的长期神经病变时，神经毒剂的类型和有针对性的临床神经学评估都是重要的考虑因素。周围神经病特异性儿科评估工具的进一步开发将有助于神经保护和康复策略的研究。
IMPORTANCE In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors.OBJECTIVE To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations.DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation.EXPOSURES Chemotherapy agents known to be toxic to peripheral nerves.MAIN OUTCOMES AND MEASURES The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures,RESULTS Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion, Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 53 of 100 participants (53.0%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 mu V; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids.CONCLUSIONS AND RELEVANCE Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted longterm, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.