Blood biomarkers for neuroaxonal injury and astrocytic activation in chemotherapy-induced peripheral neuropathy

Abstract

Background and purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer. Materials and methods: Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) every 3 weeks × 3, followed by weekly paclitaxel 80 mg/m² × 9–12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20. Results: Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN. Interpretation: NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.

Keywords

• chemotherapy
• neurofilament
• biomarkers
• neuropathy