Chemotherapy-induced peripheral neuropathy in long-term survivors of childhood cancer clinical, neurophysiological, functional, and patient-reported outcomes

Abstract

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 μV; 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 long term, 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.