The promise of serum neurofilament light as a future primary outcome target in clinical trials testing oxaliplatin-induced peripheral neurotoxicity interventions

Chemotherapy-induced neurotoxicity (CIPN) poses a major health risk for cancer survivors. CIPN is experienced by nearly all patients (94%) who receive oxaliplatin, but in varying degrees of severity and chronicity. While we know that CIPN is pervasive and disabling, no effective preventive interventions for high-risk patients exist. Future intervention research will benefit from identification of objective clinical biomarkers that can detect clinically important changes in CIPN resulting from an effective intervention. The purpose of this pilot study was to validate a promising CIPN biomarker, serum neurofilament light chain (sNfL), for use as an objective outcome measure in future oxaliplatin-induced CIPN prevention trials. The study objective was addressed using a prospective, longitudinal, descriptive design. Eligible patients had stage II-III colorectal cancer, were ≥ 18 years of age, had a Karnofsky performance status score ≥ 70, and were scheduled to receive oxaliplatin-containing adjuvant treatment regimens. At each of four timepoints, CIPN was assessed using the Total Neuropathy Score-Nurse (TNSn©), and a validated patient-reported outcome measure, the CIPN6. To quantify sNfL levels, we collected 5 mL of whole blood at each timepoint. Twenty-eight patients participated in the study; most were male (n = 19, 67.9%) and Caucasian (n = 22, 78.6%). There were statistically significant changes over time across all three CIPN measures (TNSn©, CIPN6, sNfL). sNfL values were significantly and moderately correlated with 3-month TNSn© (r = 0.51, p = 0.04) and CIPN6 scores (r = 0.58, p = 0.01). These data provide preliminary evidence of sNfL validity as an objective measure of oxaliplatin-induced CIPN.