Serum neurofilament light chain levels as biomarker of paclitaxel-induced cognitive impairment in patients with breast cancer: a prospective study.

Objective: To prospectively assess the utility of serum neurofilament light chain (sNfL) levels in identifying the risk to develop chemotherapy-induced cognitive impairment (CICI) in cancer patients. We also examined if sNfL can be identified as an early biomarker of CICI development.

Methods: We longitudinally measured sNfL levels in 20 female patients with breast cancer, scheduled to receive the 12 weekly paclitaxel-based regimen. An equal number of age-matched female heathy subjects was incuded as control group. CICI was graded by means of the Montreal Cognitive Assessment scale (MOCA); peripheral neurotoxicity (PN) was graded using the neurosensory Common Criteria for Adverse Events (CTCAE)v5.0, while sNfL levels were quantified using a high-sensitive technique (Quanterix, Simoa) before the administration of chemotherapy (T0), after 3 courses (T1), and at the end of chemotherapy (T2).

Results: Pre-treatment sNfL levels were comparable in patients and controls (p = 0.103). At T2, 5/20 patients (mean age 61.4 ± 5.0 years) developed CICI. These 5 patients also had clinically-significant PN. Patients with and without CICI had comparable sNfL values at T2 (p = 0.1). In addition, at T2, sNfL levels did not correlate significantly with MOCA score in CICI patients (p = 0.604). The difference of sNfL levels between T1 and T0 failed to predict independently the occurrence of CICI at T2.

Conclusion: Our findings do not support the utility of measuring sNfL levels as a biomarker of CICI. Grade 2-3 PN most strongly confounded our outcomes. Considering the small sample size, which might have prevented the results from being extrapolated, further testing in larger studies is warranted.