OBJECTIVE In the context of increasing numbers of childhood cancer survivors (CCS), this study aimed to enhance understanding of the biophysical basis for long term chemotherapy induced peripheral neuropathy from different chemotherapy agents in CCS. METHODS Detailed cross-sectional neurophysiological examination, using median nerve axonal excitability studies, alongside clinical assessments, in 103 long term CCS (10.5 ± 0.6 years post-treatment). RESULTS Cisplatin treated CCS (n = 16) demonstrated multiple sensory axonal excitability changes including increased threshold (P < 0.05), alterations in depolarising and hyperpolarising threshold electrotonus (P < 0.05) and reduction in resting and minimum IV slope (P < 0.01). Vincristine treated CCS (n = 73) were comparable to controls, except for prolonged distal motor latency (P = 0.001). No differences were seen in the non-neurotoxic chemotherapy group (n = 14). Abnormalities were more evident in the cisplatin subgroup with greater clinical neuropathy manifestations. CONCLUSION Persistent long term changes in axonal biophysical properties vary with different chemotherapy agents, most evident after cisplatin exposure. Longitudinal studies of nerve function during chemotherapy treatment are required to further evaluate these differences and their mechanistic basis. SIGNIFICANCE This study provides a unique biophysical perspective for persistent cisplatin related neurotoxicity in children, previously under recognised.

中文翻译：

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神经毒性化疗后儿童癌症幸存者长期周围神经生物物理特性的变化

目的 在儿童癌症幸存者 (CCS) 数量不断增加的背景下，本研究旨在加深对 CCS 中不同化疗药物长期化疗引起的周围神经病变的生物物理基础的理解。方法 在 103 名长期 CCS（治疗后 10.5 ± 0.6 年）中，使用正中神经轴突兴奋性研究以及临床评估进行详细的横断面神经生理学检查。结果 顺铂治疗的 CCS (n = 16) 表现出多种感觉轴突兴奋性变化，包括阈值增加 (P < 0.05)、去极化和超极化阈值电紧张的改变 (P < 0.05) 以及静息和最小 IV 斜率降低 (P < 0.01)。长春新碱治疗的 CCS (n = 73) 与对照组相当，但远端运动潜伏期延长 (P = 0.001)。在非神经毒性化疗组（n = 14）中没有发现差异。顺铂亚组的异常更明显，具有更多的临床神经病变表现。结论 轴突生物物理特性的持续长期变化因不同的化疗药物而异，在顺铂暴露后最为明显。需要对化疗期间的神经功能进行纵向研究，以进一步评估这些差异及其机制基础。意义 本研究为儿童中持续存在的顺铂相关神经毒性提供了独特的生物物理学视角，此前人们对此并不了解。结论 轴突生物物理特性的持续长期变化因不同的化疗药物而异，在顺铂暴露后最为明显。需要对化疗期间的神经功能进行纵向研究，以进一步评估这些差异及其机制基础。意义 本研究为儿童中持续存在的顺铂相关神经毒性提供了独特的生物物理学视角，此前人们对此并不了解。结论 轴突生物物理特性的持续长期变化因不同的化疗药物而异，在顺铂暴露后最为明显。需要对化疗期间的神经功能进行纵向研究，以进一步评估这些差异及其机制基础。意义 本研究为儿童中持续存在的顺铂相关神经毒性提供了独特的生物物理学视角，此前人们对此并不了解。