Multimodal Assessment of Cryotherapy for Paclitaxel-Induced Neuropathy

The Total Neuropathy Score-Nurse Version (TNSn) is a clinician-administered composite measure of chemotherapy-induced peripheral neuropathy. It comprises 5 items (sensory symptoms, motor symptoms, autonomic symptoms, pin-prick sensibility and vibration sensibility), each scored from 0 to 4 and summed to yield a total score ranging from 0 (minimum, no neuropathy) to 20 (maximum, most severe neuropathy); higher scores indicate a worse outcome. For each participant, the change from baseline is calculated as the TNSn total score at 6 months after completion of chemotherapy minus the TNSn total score at baseline. Positive values indicate worsening of neuropathy. The outcome is summarized per arm as the mean change with standard deviation.

Peak-to-peak amplitude of the dorsal sural sensory nerve action potential (SNAP), measured in microvolts (µV) by sensory nerve conduction study on the non-dominant lower limb with surface electrodes (2-channel EMG). For each participant, the change from baseline is calculated at each post-baseline time point as the amplitude at that time point minus the baseline amplitude. Negative values indicate a decrease in amplitude compared with baseline; lower amplitudes indicate greater sensory nerve dysfunction (axonal loss). The outcome is summarized per arm as the mean change with standard deviation.

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Serum neurofilament light chain (NfL) concentration, measured in pg/mL by single-molecule array (Simoa) immunoassay as a biomarker of neuroaxonal damage. For each participant, the change from baseline is calculated as the post-baseline value minus the baseline value. Higher concentrations indicate greater neuroaxonal injury. The outcome is summarized per arm as the mean change with standard deviation.

The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale is a validated patient-reported questionnaire assessing chemotherapy-induced neurotoxicity. It comprises 11 items, each rated from 0 to 4 and scored according to the FACIT manual to yield a subscale score ranging from 0 (minimum) to 44 (maximum); lower scores indicate more severe neurotoxicity (worse outcome) and higher scores indicate fewer symptoms (better outcome). For each participant, the change from baseline is calculated at each post-baseline time point as the subscale score at that time point minus the score at baseline. Negative values indicate worsening of patient-reported neurotoxicity. The outcome is summarized per arm as the mean change with standard deviation.

Peak-to-peak amplitude of sensory nerve action potentials (SNAP), measured in microvolts (uV) by sensory nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, the change from baseline is calculated at each post-baseline time point as the amplitude at that time point minus the baseline amplitude. Negative values indicate a decrease in amplitude compared with baseline; lower amplitudes indicate greater sensory nerve dysfunction. Results will be reported separately for each nerve assessed (sural nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.

Peak-to-peak amplitude of compound muscle action potentials (CMAP), measured in millivolts (mV) by motor nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, the change from baseline is calculated at each post-baseline time point as the amplitude at that time point minus the baseline amplitude. Negative values indicate a decrease in amplitude compared with baseline; lower amplitudes indicate greater motor nerve dysfunction. Results will be reported separately for each nerve assessed (peroneal nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.

Sensory nerve conduction velocity, measured in metres per second (m/s) by sensory nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, the change from baseline is calculated at each post-baseline time point as the conduction velocity at that time point minus the baseline velocity. Negative values indicate slowing of conduction compared with baseline; lower velocities indicate greater sensory nerve dysfunction. Results will be reported separately for each nerve assessed (dorsal sural nerve, sural nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.

Motor nerve conduction velocity, measured in metres per second (m/s) by motor nerve conduction study on the non-dominant side with surface electrodes (2-channel EMG). For each participant and each nerve, the change from baseline is calculated at each post-baseline time point as the conduction velocity at that time point minus the baseline velocity. Negative values indicate slowing of conduction compared with baseline; lower velocities indicate greater motor nerve dysfunction. Results will be reported separately for each nerve assessed (peroneal nerve, ulnar nerve). The outcome is summarized per arm as the mean change with standard deviation.

The Total Neuropathy Score-Nurse Version (TNSn) is a clinician-administered composite measure of chemotherapy-induced peripheral neuropathy comprising 5 items, each scored from 0 to 4 and summed to yield a total score ranging from 0 (minimum, no neuropathy) to 20 (maximum, most severe neuropathy); higher scores indicate a worse outcome. For each participant, the change from baseline is calculated at each post-baseline time point as the TNSn total score at that time point minus the baseline score. Positive values indicate worsening of neuropathy. The outcome is summarized per arm as the mean change with standard deviation.