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Serum neurofilament levels correlate with electrodiagnostic evidence of axonal loss in paclitaxel-induced peripheral neurotoxicity

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Abstract

Introduction

Paclitaxel-induced peripheral neurotoxicity (PIPN) typically manifests as a predominantly sensory axonopathy. Nerve conduction studies (NCS) represent the gold standard method to quantify axonal impairment in PIPN. Serum neurofilament light chain (sNfL) levels are emerging biomarkers for quantifying axonal damage in peripheral neuropathies. To date, the association between NCS abnormalities and sNfL levels during paclitaxel-based chemotherapy has not been specifically addressed.

Methods

We prospectively conducted longitudinal measurement of sNfL levels in 27 chemotherapy-naïve breast cancer patients and correlated conventional NCS recordings with sNfL in 22 of them, before (T0) and after (T1) 12 cycles of weekly paclitaxel-based therapy.

Results

PIPN was diagnosed in 24/27 patients (88%) after completion of the 12-week paclitaxel-based chemotherapy regimen. Serum NfL levels (pg/mL) were significantly higher at T1 compared to T0 (T0: 18.50 ± 12.88 vs T1: 255.80 ± 194.16; p < 0.001). The increase of sNfL levels at T1 significantly correlated with the decrease or abolishment of amplitudes recorded from the sural nerve (r = 0.620; p = 0.0035), sensory radial (r = 0.613; p = 0.005), sensory ulnar (r = 0.630; p = 0.005), and peroneal motor (r = 0.568; p = 0.024) nerves.

Conclusion

sNfL levels proportionally increase during chemotherapy administration and significantly correlate with NCS axonal abnormalities in patients with PIPN. A multimodal testing approach employing both sNfL and NCS might improve the PIPN diagnostic accuracy.

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Acknowledgements

R.V. has received support from the Instituto de Salud Carlos III (ISCIII), through the project PI20/00283 (Co-funded by the European Regional Development FUND-ERDF); S.P. has received support from the ISCIII (PI20/00544); and J.B. from the Department of Health of the Government of Catalonia CERCA Program (SLT008/18/00028) and from ISCIII (PI21/00181). We also thank CERCA Programme /Generalitat de Catalunya for institutional support.

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Authors and Affiliations

  1. Unit of Neuro-Oncology, Hospital Universitari de Bellvitge. Catalan Institute of Oncology-L’Hospitalet, Carrer de La Feixa Llarga, s/n, 08907 L’Hospitalet de Llobregat, Barcelona, Spain

    R. Velasco, C. Marco & J. Bruna

  2. Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, Bellaterra, Spain

    R. Velasco, J. Hernández & J. Bruna

  3. Neurology Department, Agios Andreas General Hospital of Patras, Patras, Greece

    A. A. Argyriou

  4. Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy

    S. Mariotto & S. Ferrari

  5. Department of Medical Oncology, Breast Cancer Unit, ICO L’Hospitalet (IDIBELL), Barcelona, Spain

    A. Stradella & S. Pernas

Authors
  1. R. Velasco
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  2. A. A. Argyriou
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  3. C. Marco
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  4. S. Mariotto
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  9. J. Bruna
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Contributions

All authors made substantial contributors to design, and/or acquisition of data, and/or analysis and interpretation of data. Individual contributors: conceived of study and design: RV, AA, JB. Performed research: all authors. Acquisition, analysis, and interpretation data: all authors. Manuscript writing: RV, AA, and JB. Revising the manuscript for important intellectual content: all authors.

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Correspondence to R. Velasco.

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Conflict of interest

Authors report no disclosures relevant to the manuscript. SM reports support for attending scientific meetings by Merck and Euroimmun and speaker honoraria from Biogen and Novartis. S.P. has served as an advisor/consultant for AstraZeneca, Daiichi Sankyo, Eisai, Novartis, Polyphor, Roche, Pierre-Fabre, SeattleGenetics, and Pfizer.

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Velasco, R., Argyriou, A.A., Marco, C. et al. Serum neurofilament levels correlate with electrodiagnostic evidence of axonal loss in paclitaxel-induced peripheral neurotoxicity. J Neurol 270, 531–537 (2023). https://doi.org/10.1007/s00415-022-11377-4

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  • DOI: https://doi.org/10.1007/s00415-022-11377-4

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