Predicting taxane-induced peripheral neuropathy by nailfold capillaroscopy: The CAPNEU pilot study

Taxane-induced peripheral neuropathy (TIPN) remains a frequent, dose-limiting toxicity in breast cancer, and reliable pre-treatment predictors are lacking. Nailfold capillaroscopy (NFC) offers a non-invasive window into systemic microvascular morphology, which may reflect vascular susceptibility relevant to neuropathy risk. The objective of the study was to evaluate whether baseline NFC morphology is associated with taxane-related neuropathy severity and symptom burden, and to explore ROC-derived thresholds of NFC parameters for identifying clinically significant neuropathy.

In this pilot cohort (N = 48) of breast cancer patients receiving taxane-based regimens (docetaxel [DOC], paclitaxel [PAC], or carboplatin-paclitaxel [CPAC]), baseline NFC parameters-capillary density (CD), capillary width (CW), capillary loop diameter (CLD), and capillary length (CL)-were recorded. Neuropathy outcomes were assessed longitudinally using NCI-CTCAE score and EORTC QLQ-CIPN20. Regimen-stratified associations were examined using Spearman's correlation. ROC analyses were conducted in the overall cohort using NCI ≥ 2 vs 0-1 as the binary endpoint; optimal cut-offs were defined by Youden's index.

Regimen-specific patterns were observed. In CPAC (N = 13), CD correlated with NCI (ρ = 0.567, p = 0.043) and CIPN20 (ρ = 0.608, p = 0.028). In PAC (N = 16), no significant correlations were found between NFC parameters and neuropathy outcomes (all p > 0.05), although CIPN20 and NCI remained strongly correlated (ρ = 0.778, p < 0.001) and CLD-NCI showed a trend (ρ = 0.486, p = 0.056). In DOC (N = 19), CL correlated with NCI (ρ = 0.509, p = 0.026) and CIPN20 (ρ = 0.484, p = 0.036), while CW was inversely correlated with CIPN20 (ρ =  - 0.510, p = 0.026). In overall ROC analyses, optimal thresholds for predicting NCI ≥ 2 were CD ≥ 8.5 capillaries/mm (sensitivity 77.3%, specificity 42.3%), CW ≥ 31.0 (90.9%, 26.9%), CLD ≥ 18.45 (90.9%, 42.3; highest Youden index 0.332), and CL ≥ 160.1 (72.7%, 46.2).

Baseline NFC morphology demonstrated regimen-dependent associations with taxane-related neuropathy outcomes and yielded exploratory ROC thresholds for identifying clinically significant neuropathy (NCI ≥ 2). CLD showed the strongest overall discrimination, while subgroup analyses highlighted distinct candidate markers (CD in CPAC; CL in DOC). These findings are hypothesis-generating and warrant validation in larger, independent cohorts.