Quantitative assessment of proprioceptive dysfunction in cancer survivors post oxaliplatin-containing chemotherapy.

Abstract

e24071 Background: Oxaliplatin (OX) is commonly used for gastrointestinal cancers but can cause chronic neurotoxicity with long-term motor impairments (e.g. dexterity loss, poor balance, and falls). These impairments are often attributed to OX-induced sensory neuropathy that disrupts touch, vibration, and proprioception in distal limbs. However, some cancer survivors report motor impairments even in the absence of sensory neuropathy. Recent animal studies suggest OX induces global signaling dysfunction in muscle proprioceptors that may account for the motor impairments in the absence of sensory neuropathy. However, this mechanism has yet to be investigated in cancer survivors. We hypothesize that cancer survivors will display impaired proprioceptive function compared to age-matched healthy controls using quantitative techniques that are more sensitive than current clinical measures. Methods: We assessed use of proprioception for controlling upper extremity position, force, and posture using target reaching, force matching, and postural stability tasks, respectively. A haptic robot quantified motor performance in all tasks, performed with and without visual feedback to disambiguate proprioceptive from vision. The dominant hand and wrist were fixed in an orthosis emphasizing elbow and shoulder use since these joints are less likely to have sensory neuropathy. Self-reported symptoms and functional limitations were measured with the QLQ-CIPN20 questionnaire. Accuracy and trial-to-trial variability for each task were compared between cancer survivors and controls using linear mixed effect models. Results: Thirteen cancer survivors (0 – 20 months post OX-treatment) and 7 controls completed the study. Without visual feedback, cancer survivors had significantly decreased accuracy (p < 0.001) and increased trial-to-trial variability (p < 0.05) in all tasks compared to controls. Deficits in force matching were correlated with self-reported motor dysfunction on the QLQ-CIPN20 (r = 0.87, p < 0.001). Conclusions: Proprioceptive deficits occur in cancer survivors who received OX-treatment and are associated with motor dysfunction. This identified mechanism of motor impairment may present opportunities for targeted interventions.