Prospective assessment of serum neurofilament light chain in platinum-induced and taxane-induced peripheral neuropathy

TL;DR

This study investigates whether serum neurofilament light chain levels can predict chemotherapy-induced peripheral neuropathy severity and outcomes in cancer patients.

Contribution

The study prospectively assesses sNfL as a biomarker for platinum- and taxane-induced neuropathy and links it to clinical outcomes.

Findings

Taxanes caused higher and sharper sNfL increases compared to platinum agents.

Age-adjusted sNfL correlated with neuropathy severity in platinum-treated patients.

sNfL levels did not detect early axonal damage before clinical signs in most patients.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially disabling complication of the neurotoxic chemotherapies; however, its occurrence is often unpredictable. We aimed to determine whether serum levels of neurofilament light chain (sNfL) could predict the onset and severity of CIPN, and whether sNfL levels were associated with other clinical factors in people with cancer.

Adult patients (>18 years) prescribed at least four cycles of oxaliplatin, cisplatin, docetaxel or paclitaxel were clinically assessed and had blood taken for sNfL analysis at baseline and prior to each cycle. Peak sNfL was compared with clinical characteristics and Total Neuropathy Score-Clinical version (TNSc), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, V.4.03) and CIPN-Rasch-built Overall Disability Scale (CIPN-RODS). Individual patient trends in sNfL and TNSc were examined.

42 patients completed the study, with 36 receiving platinum agents and 6 receiving taxanes. Peak sNfL was higher with taxanes than with platinum agents (129.9 vs 31.0 pg/mL; p<0.0001). Higher peak sNfL was not associated with final TNSc, CTCAE or CIPN-RODS in patients receiving platinum agents. Using age-adjusted NfL z-scores, peak sNfL was associated with CIPN-RODS (rs=−0.45; p=0.012) and was higher in patients with a final CTCAE Grade of 2 compared with Grades 0–1 (p=0.015) but was not associated with final TNSc (rs=+0.37, p=0.050). In patients receiving platinum agents, higher peak sNfL was associated with death within 6 months of study entry (p=0.020). sNfL rose in conjunction with the increase in TNSc but did not precede clinical symptoms/signs of neuropathy in most patients.

Taxanes cause greater and sharper sNfL rises than platinum agents. Age-adjusted sNfL associates with neuropathy severity in platinum-treated patients; however, in most patients it is unable to detect early axonal damage before this is detectable with clinical examination.

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