Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is caused by drug-induced damage to the axons which is not detected easily due to lack of reliable, clinically applicable modalities. Diffuse tensor imaging (DTI) allows for quantitative measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), which have been shown to detect nerve injury by Magnetic Resonance Imaging (MRI).
Methods: We sought to evaluate if DTI could be used for detection of CIPN in patients with breast cancer treated with a taxane. Patients with h/o exposure to neurotoxic chemotherapy, diabetes, or peripheral neuropathy were excluded. Patients completed pre- and post-chemotherapy MRI of bilateral legs and FACT&GOG-Ntx. Genotyping of single-nucleotide variations (SNVs) was performed to detect known associations with CIPN.
Results: We had 14 evaluable patients in this prospective trial. Mean FA values post-chemotherapy were significantly lower than baseline at mid-calf (p < 0.0001) and ankle (p = 0.03). We did not find any significant change in mean ADC values. In patients without symptomatic neuropathy, mean FA values decreased more than symptomatic patients at mid-calf (p < 0.001). Of the 41 genotyped SNVs, only rs8110536 was found to be significantly associated with development of CIPN.
Conclusions: Our results show that FA values are indicative of CIPN and differential changes in FA values in symptomatic versus asymptomatic patients highlights its potential to be further studied as a predictive biomarker for CIPN. This is the first study to highlight a non-invasive, imaging based, objective biomarker which, if validated, can be translated into clinic easily.
Keywords: Apparent diffusion coefficient; Breast cancer; Chemotherapy-induced peripheral neuropathy; Diffuse tensor imaging; Fractional anisotropy.