Abstract
Chemotherapy-induced neurotoxicity is an increasingly recognized clinical issue in oncology. in vivo confocal microscopy (IVCM) of corneal nerves has been successfully used to diagnose peripheral neuropathies, including diabetic neuropathy. The purpose of this study was to test if the combination of corneal nerve density and morphology assessed by IVCM is useful to monitor the neurotoxic effects of chemotherapy compared to epidermal nerve quantification. Overall, 95 adult patients with different cancer types were recruited from the oncology and hematology departments of the San Raffaele Hospital. Neurological examination, including clinical Total Neuropathy Score, and in vivo corneal confocal microscopy (IVCM), were performed before and after chemotherapy. In a group of 14 patients, skin biopsy was performed at the first and last visit. In the group of 14 patients who underwent both skin biopsy and corneal nerve imaging, clinical worsening (+69%, p = 0.0018) was paralleled by corneal nerve fiber (CNF) density reduction (−22%, p = 0.0457). Clinical Total neuropathy score significantly worsened from the first to the last visit (+62%, p < 0.0001). CNF length was not significantly reduced overall. However, CNF density/tortuosity ratio significantly decreased after therapy. Correlation analysis showed that the CNF density/tortuosity ratio was also correlated with the number of chemotherapy cycles (r = −0.04790, P = 0.0009). Our data confirm that in vivo corneal confocal microscopy is a helpful, non-invasive tool which shows promise for the diagnosis of chemotherapy-induced peripheral neuropathies. IVCM could allow a rapid, reproducible and non-invasive quantification of peripheral nerve pathology in chemotherapy-associated neuropathy.
Highlights
Chemotherapy-induced neurotoxicity is one of the most common side effects of cancer treatment
CTNS significantly worsened from the first to last visit (+62%, p < 0.0001, Figure 1A). clinical Total Neuropathy Score (cTNS) worsened significantly after treatment with Paclitaxel (p = 0.0029), Platinum compounds (p = 0.0138), and in combination with Cyclophosphamide (p = 0.0428), while no significant difference was found in the VTD group (p = 0.1872, Figure 1B)
We previously showed that corneal and epidermal nerve density show good correlation in an animal model of paclitaxelinduced neuropathy [23]
Summary
Chemotherapy-induced neurotoxicity is one of the most common side effects of cancer treatment. It has been recognized as a major determinant of functional impairment, increased pain, and reduced quality of life [1, 2]. Paclitaxel, for instance, can induce mild to moderate neuropathy in 93% of treated patients, which progresses to severe in 25% of them [3,4,5]. Platinum compounds lead to chemotherapy-induced peripheral neuropathy (CIPN) in up to 50% of the patients [6,7,8]. CIPN has been reported following Bortezomib, with a prevalence ranging from 38 to 53%, and after thalidomide, with a frequency of 63% [8, 9]. Cyclophosphamide has been reported to have neurotoxic effects on both younger and elderly patients [7, 10]
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