Purpose: Chemotherapy induced peripheral neurotoxicity (CIPN) is a common side effect of cancer treatment that typically manifests as sensory neuropathy and produces degeneration of peripheral axons. Serum neurofilament light chain (NfL) is a potential protein biomarker of axonal degeneration which has been recently investigated as a promising method to identify individuals at risk of CIPN. This study aimed to identify longitudinal changes in NfL in association with CIPN development, in patients receiving the neurotoxic chemotherapy paclitaxel.
Method: Patients were assessed at three timepoints – beginning, middle and end of paclitaxel treatment. CIPN was assessed using a clinical grading scale (National Cancer Institute -Common Terminology for Adverse Effects (CTCAE) neuropathy scale), neurological grading scale (Total Neuropathy Score TNS clinical version) and patient reported outcome measures (EORTC- CIPN20). Serum samples were collected at the same time points and serum NfL was quantified using Quanterix SIMOA immunoassay.
Results: A total of 67 paclitaxel-treated patients (98% female, mean age 56±1.6 years) were recruited. Neuropathy incidence and severity increased over the course of treatment (p<0.001). By the end of treatment, 88% (n=59) had developed CIPN, which was mild in 55% (n=37, grade 1) and moderate/severe in 32% (n=22, grade 2/3). There was a significant increase between NfL from patients assayed prior to cycle 1 (n=36) and those assayed prior to cycle 2 paclitaxel (n=31; p=.0002). NfL mean concentration was significantly increased from beginning of treatment (45.2±16.1 pg/mL) to mid-treatment (151±18.5 pg/mL, p<0.001) and to end of treatment (191±16.0 pg/mL, p<0.001). NfL levels at baseline and interim were significantly correlated with TNS score at baseline (r=0.283, p=0.02) interim (r=0.396, p=0.004) respectively.
Conclusion: Serum NfL levels increased during paclitaxel treatment, in line with increasing CIPN severity. Quantification of serum NfL may provide a clinically useful marker of emerging neurotoxicity in patients who are vulnerable to CIPN.