Oxaliplatin Neuropathy: Predictive Values of Skin Biopsy, QST and Nerve Conduction

Abstract

Background: Oxaliplatin-induced peripheral neuropathy negatively affects the quality of life for patients with gastrointestinal cancers and may cause neuropathic pain. Measures of peripheral nerve structure or function, such as intraepidermal nerve fiber density (IENFD) during treatment could reduce neuropathy severity through individualized dose reduction. Objective: The aim was to evaluate the predictive values of IENFD, quantitative sensory testing (QST), and nerve conduction studies (NCS) for significant neuropathy and neuropathic pain. Methods: Fifty-five patients were examined prospectively before, during, and six months following treatment using skin biopsies, QST and NCS. Clinically significant neuropathy six months after treatment was defined as reduced Total Neuropathy Score of more than five and neuropathic pain was assessed according to International Association for the Study of Pain criteria. Results: Thirty patients had a clinically significant neuropathy, and 14 had neuropathic pain. Vibration detection threshold (VDT) before treatment was correlated with clinically significant neuropathy six months after treatment (OR 0.54, p = 0.01) and reductions in cold detection threshold (CDT) after 25% of treatment (OR 1.38, p = 0.04) and heat pain threshold (HPT) after 50% of treatment (OR 1.91, p = 0.03) with neuropathic pain. Cut off values of 5 for baseline VDT and changes of more than –0.05 °C and –0.85 °C in CDT and HPT were estimated. Sensitivity and specificity was low to moderate. There was no correlation between changes in IENFD or NCS and significant neuropathy or neuropathic pain. Conclusions: Vibration detection thresholds and thermal detection thresholds may be useful for prediction of clinically significant and painful neuropathy, respectively. However, low to moderate sensitivity and specificity may limit the predictive value in clinical practice.

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

“…Several longitudinal studies, including NCS during OXA therapy, have showed a significant progressive decrease in sensory nerve action potentials (SNAPs) and preservation of motor action compound (CMAPs), in keeping with the presence of an axonal sensory neuropathy, and consistent with the clinical symptoms and signs worsening during the treatment [17,41,[58][59][60][61][62][63][64]. NCS are capable of objectively assessing the extent of peripheral nerve damage and may also facilitate the identification of patients that manifest subclinical peripheral neuropathy prior to the onset of clinically significant neurotoxicity.…”

“…The assessment of sural nerve instead dorsal sural (Figure 2), and the size of the study could underlie these negative findings. Long-term longitudinal neurophysiological assessments of OXA-treated patients have revealed a significant recovery of the SNAPs in sensory nerves in some studies [58,63,71] but not in other studies [59,61]. The length of follow-up observation may explain these differences.…”

“…Very recently, Kroigard et al identified VDT measure obtained before treatment correlated as a predictor of clinically significant OX-AIPN six months post-treatment. However, sensitivity of a baseline VDT < 5 (maximum 8) for the prediction of clinically significant neuropathy six months after treatment was modest (76.0% (95% CI 54.9% to 90.6%)) and specificity was low (53.3% (95% CI 34.3% to 71.7%)) [59]. Muscle sampling with needle electromyography (nEMG) can show repetitive myokymic discharges and neuromyotonic runs within 1-4 days after the first OXA administration [72][73][74].…”

“…in predicting the occurrence of clinically significant OXAIPN in 55 CRC patients [59]. The assessment of sural nerve instead dorsal sural (Figure 2), and the size of the study could underlie these negative findings.…”

“…In this line, reductions of the SNAPs of >11.5% in the median nerve between baseline and four cycles of OXA (odds ratio = 5.603, p = 0.031) and of >22.5% in the sural nerve between four and eight cycles of chemotherapy (odds ratio = 5.603, p = 0.031) were independently associated with the risk of developing severe OXAIPN [63]. However, very recently, negative results were obtained in another study evaluating the role of the sural nerve after administering 25% or 50% of the planned OXA dose in predicting the occurrence of clinically significant OXAIPN in 55 CRC patients [59]. The assessment of sural nerve instead dorsal sural (Figure 2), and the size of the study could underlie these negative findings.…”