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Abstract
PurposeOxaliplatin-induced peripheral neuropathy (OIPN) is a chronic, debilitating late effect following oxaliplatin treatment. Neurofilament light chain (NfL) is a structural protein found in nerve axons that was investigated upon oxaliplatin exposure in vitro and in vivo correlated to symptoms of OIPN in colorectal cancer patients receiving oxaliplatin.MethodsHuman sensory neurons, derived from induced pluripotent stem cells, were exposed to clinically relevant concentrations of oxaliplatin in vitro, with NfL concentrations measured in the cell medium. The prospective clinical study included patients with colorectal cancer undergoing chemotherapy therapy with or without oxaliplatin. Possible OIPN was defined as bilateral presence of numbness and/or presence of pricking sensations in the feet documented in an interview at the time of blood sampling prior to, 3, and 6 months after initiating treatment.ResultsOxaliplatin exposure led to a dose-dependent NfL increase in vitro. In the clinical cohort of 30 patients (18 in the oxaliplatin group), NfL levels rose at 3 and 6 months compared to controls. NfL level changes correlated to OIPN symptoms at the 6-month timepoint (rho 0.81, p < 0.001). However, the interindividual variation was substantial, and most patients showed only a minor increase in NfL.ConclusionBoth in vitro and clinical data indicate that oxaliplatin exposure results in elevated NfL levels. Further prospective studies are needed to evaluate NfL as an early biomarker for OIPN, specifically focusing on the timing of blood sampling during chemotherapy treatment to enable the timely reduction of oxaliplatin.
Published Version
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