Neurofilament light chain as a biomarker of axonal damage in sensory neurons and paclitaxel-induced peripheral neuropathy in patients with ovarian cancer

Christina Mortensen, Karina Dahl Steffensen, Emma Simonsen, Kamille Herskind, Jonna Skov Madsen, Dorte Aalund Olsen, Ditte Bork Iversen, Troels Korshøj Bergmann, Anton Pottegård, Tore Bjerregaard Stage*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) exposed to paclitaxel. Serum NFL (sNFL) levels were quantified in 190 patients with ovarian cancer receiving paclitaxel/carboplatin chemotherapy at baseline and after each of the following 2 or 6 cycles. Adverse outcomes related to PIPN were retrospectively obtained, and Cox regression model was performed with different sNFL cut-offs after first cycle. The apparent elimination half-life of sNFL was estimated in patients who discontinued paclitaxel. Paclitaxel neurotoxicity in iPSC-SNs was accompanied by NFL release in a concentration-dependent manner ( P < 0.001, analysis of variance). Serum NFL levels increased substantially in patients during paclitaxel/carboplatin chemotherapy with considerable interindividual variability. Patients with sNFL >150 pg/mL after first cycle had increased risk to discontinue paclitaxel early (unadjusted HR: 2.47 [95% CI 1.16-5.22], adjusted HR: 2.25 [95% CI: 0.88-5.79]). Similar trends were shown for risk of severe PIPN and paclitaxel dose reduction because of PIPN. The median elimination half-life of sNFL was 43 days (IQR 27-82 days). Neurofilament light chain constitutes an objective biomarker of neurotoxicity in iPSC-SNs and in ovarian cancer patients with high sNFL predicting PIPN-related adverse outcomes. If prospectively validated, NFL can be used to study PIPN and may guide clinical decision making and personalize treatment with paclitaxel.

Original languageEnglish
JournalPain
Volume164
Issue number7
Pages (from-to)1502-1511
ISSN0304-3959
DOIs
Publication statusPublished - 1. Jul 2023

Bibliographical note

Copyright © 2022 International Association for the Study of Pain.

Keywords

  • Biomarkers
  • Carboplatin/adverse effects
  • Female
  • Humans
  • Induced Pluripotent Stem Cells
  • Intermediate Filaments
  • Neurofilament Proteins
  • Ovarian Neoplasms/drug therapy
  • Paclitaxel/adverse effects
  • Peripheral Nervous System Diseases/chemically induced
  • Quality of Life
  • Retrospective Studies
  • Sensory Receptor Cells

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