TIPN is a sensory-predominant distal axonopathy that is a major cancer survivorship issue without non-invasive objective measures to guide treatment. Skin biopsies consistently show reduced IENF density but are invasive and rarely performed. This study sought to determine whether nerve cross-sectional area (CSA) using NMUS could detect neurotoxicity in patients with TIPN. 

To utilize neuromuscular ultrasound (NMUS) for non-invasive assessment of taxane-induced peripheral neuropathy (TIPN) and correlate macroanatomic with microscopic changes in intraepidermal nerve fiber (IENF) density.

A cross-sectional study enrolled breast cancer patients with symptomatic TIPN who were receiving taxane actively, received taxane within 1 year (early), or beyond 1 year (late). The primary objectives were to compare nerve CSA of sural, tibial, and median nerves to historical controls. Secondary objectives were to correlate CSA with IENF (distal and proximal leg skin biopsies), timing of chemotherapy, and objective measures of nerve function by patient-reported symptom scale (EORTC-QLQ CIPN20) and nerve conduction studies.

19-of-20 planned patients have been enrolled and 70 nerve sites evaluated. Patients reported moderate-to-severe CIPN symptoms at a median of 3.7 months (range 0-43) since completing paclitaxel (n=10), docetaxel (8), or nab-paclitaxel (1). Distal leg IENF steadily declined in patients receiving active taxane (8.9+5/mm), early (5.7+3/mm, p=0.08), and late post-treatment (4.7+2/mm, p=0.09). While tibial CSA was similar to historical controls (p=0.26), sural sensory nerve CSA was 1.1mm² smaller (p<0.003) supporting the sensory predominance of TIPN. Older age (r=-0.74, p=0.003) and lower body mass index (r=-0.52, p=0.02) were associated with smaller sural CSA. When controlling for these factors, for each 10/mm drop in IENF, sural CSA was 1.2mm² smaller (p=0.04, R²=0.69).

This study demonstrates a link between the macro- and microanatomic changes within sensory nerves for patients with TIPN and suggests that NMUS may be a non-invasive measure of peripheral neurotoxicity from chemotherapy. Longitudinal studies are ongoing.