Gait as a Quantitative Indicator of the Severity of Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study

Gait as a Quantitative Indicator of the Severity of Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Gait as a Quantitative Indicator of the Severity of Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study Serena Jiyeon Kim, Patrick Dougherty, Salahadin Abdi, Saba Javed This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6666978/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Mar, 2026 Read the published version in Supportive Care in Cancer → Version 1 posted 10 You are reading this latest preprint version Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating side effect of neurotoxic chemotherapeutic agents. Patient-reported outcome (PRO) measures are widely utilized to assess CIPN severity; however, they are subject to bias and variability. This prospective case series investigates whether gait parameters provide an objective measure of CIPN severity. This pilot study consisted of 27 patients: 9 active CIPN, 9 CIPN resolved, and 9 healthy controls. Gait parameters including velocity, ambulation time, cadence, distance, and number of steps were assessed using GAITRite®. Treatment-Induced Neuropathy Assessment Scale (TNAS) pain and PROMIS® 29+2 Profile v2.1 (PROPr) scores were collected and correlated with gait measures. Patients with active CIPN exhibited significant gait impairments compared to both CIPN-resolved and healthy control groups. Active CIPN patients exhibited significantly slower velocity, greater step count, shorter walking distance, and longer ambulation time as compared to both CIPN-resolved and healthy control groups. Active CIPN patients also had higher cadence than healthy controls. TNAS pain scores were significantly negatively correlated with velocity and positively correlated with ambulation time in active CIPN patients. PROPr domains (pain intensity, pain interference, and physical function) were significantly correlated with velocity and ambulation time. Our preliminary findings demonstrate the potential for gait parameters to serve as an objective and relatively quick method for assessing CIPN severity. Further studies with a larger and more diverse sample will be necessary to establish gait as a clinical tool for evaluating severity, functional decline, and recovery in CIPN patients. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and prevalent side effect of neoplastic agents [ 26 ]. CIPN may occur during neurotoxic chemotherapy treatment or following its termination, i.e., “coasting,” a phenomenon associated with agents such as cisplatin and oxaliplatin [ 13 ]. The incidence of CIPN is agent-dependent and is reported to range between 11–100%, with approximately a third of patients experiencing “coasting” symptoms lasting 6 months or more after chemotherapy [ 5 , 48 ]. CIPN predominantly involves sensory neurons in a length-and-dose-dependent manner; motor and autonomic neural deficits are less common and usually observed at higher chemotherapy dosages. CIPN symptoms typically manifest in a symmetrical stocking-glove distribution with pain, paresthesias, dysesthesias, decreased sensitivity to vibration, and impaired proprioception [ 17 ]. In advanced stages, CIPN affects motor function, balance, and strength in distal extremities [ 28 , 34 , 42 , 53 ]. Due to such side effects CIPN leads to altered psychophysical characteristics such as gait abnormalities, impaired balance, postural instability and increased risk of falls [ 28 , 35 , 41 , 56 ]. Consequently, CIPN interferes with patients’ daily functioning and diminishes their quality of life and necessitates dose reduction or cessation of chemotherapy [ 3 , 22 , 32 , 55 ]. Currently, there is a lack of an objective and standardized method to measure CIPN severity. Patient-reported outcome (PRO) measures, such as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-CIPN20), are widely used to evaluate the severity and progression of CIPN. However, self-reported tools of CIPN are prone to inaccuracies due to their subjective nature and variability in symptom reporting, influenced by individual adaptation to symptoms and underreporting of symptoms due to distrust or frustration toward healthcare providers [ 4 , 47 ]. While the EORTC-CIPN20 demonstrates good interrater and test-retest reliability, it suffers from variability in patient interpretation of test items, conceptual misalignment, response bias and discrepancies from clinical evaluations [ 1 , 23 , 29 , 30 , 51 ]. In addition, placebo and nocebo effects have been reported in diabetic peripheral neuropathy (DPN) and fibromyalgia patients in which patients report moderate pain relief in randomized control trials after receiving oral placebo medications. More than half of the patients in the placebo arm also reported adverse effects [ 12 ]. Placebo effects accounted for up to 45% of active drug responses in fibromyalgia and 62% in DPN trials with a significant positive correlation between placebo and drug effects [ 16 ]. Hence, placebo and nocebo responses may further complicate assessing the effectiveness of treatment options for CIPN. As such, a reliable tool is essential for objectively assessing CIPN severity to best guide practitioners in determining optimal interventions and symptom relief strategies. The goal of this pilot study was to preliminarily test the premise that gait parameters would provide such a metric and to inform the design of future investigations on its clinical usage. Further assessment with a larger sample population is necessary to confirm the feasibility and reliability in clinical practice. Methods Recruitment This prospective case series and pilot investigation was approved by MD Anderson Institutional Review Board Protocol 2024 − 0368. A total of 27 patients between the ages 45 and 72 seen at a pain management clinic at a large cancer center in Houston, Texas between Jan. 1st, 2024 and Dec 31st, 2024 were selected for this study. CIPN status of participants was determined by clinical diagnosis and each group (CIPN active, CIPN resolved, and healthy controls) was composed of 9 patients. CIPN resolution was determined by the improvement of clinical symptoms of CIPN, such as "burning, tingling, numbness, and cold sensations," until the symptoms fully resolved. The inclusion and exclusion criteria are listed in Table 1 . Informed consent was received from all participants. The three groups were age-matched. In addition to age, other demographic data including gender and race were collected. The data collected for this study are presented in summative form. Individual data points are not publicly available to maintain patient confidentiality. They may be obtained by contacting the corresponding author with a reasonable request. Table 1 Summary of Inclusion and Exclusion Criteria Group Inclusion Criteria Exclusion Criteria Active CIPN ● Age ≥ 18 years and ≤ 85 years ● Pain score > = 5 on a scale of 0 to 10 ● Patients diagnosed with painful CIPN of lower extremity due to either vinca alkaloids or platinum-based compounds ● CIPN symptoms present for ≥ 6 months; ● Not currently undergoing chemotherapy ● Patients with cognitive dysfunction or pre-existing gait dysfunction due to underlying neurologic dysfunction ● Patient with recent history (< 6 months) of drug or alcohol abuse ● Patients with open skin lesion or undergoing antibiotic therapy for local or systemic infection ● Patients with painful diabetic peripheral neuropathy or other preexisting peripheral neuropathy CIPN resolved ● Age ≥ 18 years and ≤ 85 years ● Patients with prior clinically diagnosed history of CIPN of lower extremity, now resolved Healthy Control ● Age ≥ 18 years and ≤ 85 years ● Patients with no prior history of chemotherapy or any form of neuropathy Gait Assessment Gait assessment was conducted using the GAITRite® Walkway (GAITRite machine, CIR Systems, Sparta, NJ), a reliable tool to detect kinetic forces, time sensor activation, and measure relative distances between sensors [ 19 ]. Quantitative gait parameters including distance, ambulation time, velocity, number of steps, and cadence were recorded [ 54 ]. Treatment-Induced Neuropathy Assessment Scale (TNAS) Scores The TNAS v3.0 is a valid and reliable patient-reported outcome measure for assessing treatment-induced peripheral neuropathy (TIPN) [ 38 ]. The TNAS evaluates multiple domains: pain, tingling, numbness, hot/burning sensations, coldness, difficulty using fingers, balance/fall risk, walking difficulties, and sleep disturbances. TNAS pain scores were used to analyze their relationship with gait variables (distance, ambulation time, velocity, number of steps, and cadence). PROMIS® 29+2 Profile v2.1 (PROPr) PROPr is a patient-reported outcome measure of health-based quality of life (QOL) assessed over the following 7 domains: physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain interference. It incorporates the 29 items from the PROMIS-29 Profile v2.1 and two additional items for a more comprehensive coverage of health-related QOL. Statistical Analysis All statistical analyses in this study were generated using Jamovi, version 2.6.23 (The Jamovi Project, Sydney, Australia). Data visualization was conducted using R (version 4.4.2; R Core Team, 2023) within RStudio (Posit, 2023). Demographics A Kruskal-Wallis test was run to compare the age among the CIPN active, CIPN resolved, and healthy control groups. Fisher’s exact test was used to assess race distribution among the groups. Gait variable analyses The Shapiro-Wilk test was applied to assess normality and the Levene’s test to assess homogeneity of variances for all data: demographics, number of steps, cadence, ambulation time, distance and velocity. Kruskal Wallis was used to compare among the active CIPN, CIPN resolved, and healthy control groups. As previous literature indicates that age and gender may have a modulatory role in gait characteristics, a linear regression was performed to determine any significant relationship between the variables and gait parameters that were measured in this study [7,27,46,52]. If there was a significant relationship, an analysis of covariance (ANCOVA) was used to compare the gait variable across CIPN active, CIPN resolved, and healthy control groups. If the homogeneity of regression slopes was violated, a general linear model was used. If there was no significant relationship with age and gender and the assumptions of normality were met but not the homogeneity of variances, a Welch’s test with the Games-Howell Post-Hoc test was conducted. If neither assumption were met, a Kruskal-Wallis test with the Dwass-Steel-Critchlow-Fligner pairwise comparison was conducted. An alpha value of p < 0.05 was defined as statistically significant. Effect sizes were also calculated to provide additional context for the magnitude of group differences. Correlation Between Gait Variables and TNAS Pain Scores As the variables were normally distributed, Pearson’s correlation was used to assess the relationship between gait variables and TNAS pain scores in active CIPN patients. An alpha value of p < 0.05 was defined as statistically significant. Correlation between Gait Variables and PROMIS® 29+2 Profile v2.1 (PROPr) domains Data from all three groups (active CIPN, CIPN resolved, and healthy control) were pooled to correlate gait variables and PROPr domains. This approach allows for determining whether gait variables can serve as an objective measure across all severities/status of CIPN. For normally distributed data, Pearson’s correlation was used to assess the relationship between all the gait variables and the following PROMIS® 29+2 Profile v2.1 (PROPr) domains: pain intensity, pain interference, physical function. For non-normally distributed data, Spearman's correlation was used. An alpha value of p < 0.05 was defined as statistically significant. Results Table 2 Demographic Information of Participants (n = 27) Characteristics CIPN active (n = 9) CIPN resolved (n = 9) Healthy Controls (n = 9) p-value Sex (males/females) 4/9 4/9 4/9 1.00 Age (years) 60.4 ± 9.34 60.8 ± 9.43 59.9 ± 9.51 0.972 Race (n, %) 0.861 African American 1 (11.1%) 3 (33.3%) 3 (33.3%) Asian 1 (11.1%) 0 (0.0%) 0 (0.0%) Caucasian 3 (33.3%) 5 (55.6%) 4 (44.4%) Hispanic 2 (22.2%) 1 (11.1%) 2 (22.2%) As the number of male and female participants in each study group was equal, there was no statistical difference between the distribution of males and females ( p = 1.00) among the groups. The age distribution was also similar between each group ( p = 0.972) with the mean age of approximately 60 years old for each group. Finally, there was no significant difference in the distribution of race ( p = 0.673), which was considered as a social and cultural construct for this study (Table 2 ). Table 3 Comparison of gait parameters Gait variable CIPN active (n = 9) CIPN resolved (n = 9) Healthy Controls (n = 9) Effect size p-value M SD M SD M SD Number of steps 44.11 20.68 10.17* 2.24 7.56* + 0.73 0.755 < 0.05 H Cadence (steps / min) 204.54 99.83 75.16 7.86 58.72* 15.29 0.45 < 0.01 H Ambulation time (s) 13.11 2.03 8.22* 2.11 8.11* 1.76 0.614 < 0.001 Fa Distance (cm) 484.89 19.91 510.56* 8.35 514.44* 7.14 0.560 < 0.001 H Velocity (cm/s) 37.78 6.04 65.86* 16.67 66.67* 16.95 0.747 < 0.001 Fg Note : M indicates mean. * indicates a significant difference with the CIPN active group; + indicates a significant difference with the CIPN resolved group. H represents Kruskal-Wallis H-test; Fa represents ANCOVA F-test; Fg represents general linear model F-test. NUMBER OF STEPS The healthy control group took significantly fewer steps (7.56 ± 0.73) to complete the 16-foot mat twice than both the CIPN resolved (10.17 ± 2.24) and active CIPN groups (44.11 ± 20.68). The CIPN resolved group took significantly fewer steps compared to the active CIPN group (Table 3 , Fig. 1 ). CADENCE The CIPN active group had a significantly greater cadence (steps / minute) than the healthy controls. There was no significant difference in cadence between the healthy control and CIPN resolved participants or between CIPN resolved and active CIPN participants (Table 3 , Fig. 2 ). AMBULATION TIME The active CIPN group exhibited a significantly longer ambulation time (13.11 ± 2.03) than the CIPN resolved (8.22 ± 2.11) and healthy control (8.11 ± 1.76) group. There was no significant difference in ambulation time between the healthy control and CIPN resolved groups (Table 3 , Fig. 3 ). DISTANCE The active CIPN group travelled a significantly lesser distance (484.89 ± 19.91) than the CIPN resolved group (510.56 ± 8.35) and healthy control (514.44 ± 7.14). There was no significant difference in walking distance between CIPN resolved and healthy control groups (Table 3 , Fig. 4 ). VELOCITY The active CIPN group displayed a significantly slower velocity (37.78 ± 6.04) than the healthy controls (66.67 ± 16.95) and CIPN resolved (65.86 ± 16.67) group. However, there was no significant difference in velocity between healthy controls and those with resolved CIPN (Table 3 , Fig. 5 ). Table 4 Treatment-Induced Neuropathy Assessment Scale scores in Active CIPN patients TNAS category Mean (n = 9) SD (n = 9) Numbness 6.33 1.23 Tingling 6.56 1.24 Pain 7.56 1.13 Walking 7.67 1.50 Hot/burning 6.56 1.24 Coldness 6.56 1.24 Difficulty using fingers 6.56 1.24 Balance/fall 6.56 1.24 Sleep 8.22 0.97 Table 5 Correlation between TNAS Pain Scores and Gait Variables in Active CIPN patients Gait variable r (df = 7) p-value Number of steps -0.040 0.918 Cadence (steps / min) -0.202 0.602 Ambulation time (s) 0.788 0.012* Distance (cm) 0.303 0.428 Velocity (cm/s) -0.737 0.023* TNAS Pain Scores vs. Velocity (cm/s) in Active CIPN patients The average TNAS scores for active CIPN patients ranged between 6.33 ± 1.23 (numbness) and 8.22 ± 0.97 (sleep). The average pain score was 7.56 ± 1.13 (Table 4 ). There was a significant negative correlation between TNAS pain scores and walking velocity in Active CIPN patients (r = − 0.737, p = 0.023), indicating that higher pain scores were associated with slower walking speed (Table 5 , Fig. 6 ). TNAS Pain Scores vs. Ambulation Time (s) in Active CIPN Patients There was a significant positive correlation between TNAS pain scores and ambulation time in Active CIPN patients (r = 0.788, p = 0.012), indicating that higher pain scores were associated with longer walking times (Table 5 , Fig. 7 ). Table 6 Correlation between PROPr domains and Gait Variables in active CIPN patients, CIPN resolved patients, and healthy controls Gait variable Pain Intensity (n = 27) Pain Interference (n = 27) Physical Function (n = 27) correlation* p-value correlation p-value correlation p-value Number of steps -0.04 0.92 0.26 0.50 0.06 0.88 Cadence (steps / min) -0.20 0.60 0.06 0.89 0.21 0.58 Ambulation time (s) ρ = 0.82 0.01 ρ = 0.80 0.01 ρ = -0.82 0.01 Distance (cm) 0.30 0.43 0.21 0.59 -0.21 0.59 Velocity (cm/s) -0.73 0.02 -0.80 0.01 0.77 0.01 *unless otherwise indicated with “ ρ ” which represents Spearman’s correlation, all other correlation values represent “ r ” from Pearson’s correlation. Pain intensity Ambulation time ( ρ = 0.82, p = 0.01 was significantly positively correlated with pain intensity, indicating that individuals who experience greater pain walk for a longer period. Velocity ( r = -0.73, p = 0.02) was significantly negatively correlated with pain intensity, suggesting that individuals who experience greater pain walk slower (Table 6 , Fig. 8 ). Pain Interference Ambulation time ( ρ = 0.80, p = 0.01) was significantly positively correlated with pain interference, which aligns with the findings for pain intensity. Velocity ( r = -0.80, p = 0.01) had significantly negative correlations with pain interference (Table 6 , Fig. 8 ). Physical Function Ambulation time ( ρ = -0.82, p = 0.01) was negatively correlated with physical function, suggesting that individuals with better physical functioning have better gait characteristics such as walking for shorter periods. Velocity ( r = 0.77, p = 0.01) was positively correlated with physical function, indicating that individuals with better physical function walk faster (Table 6 , Fig. 8 ). Discussion A more reliable yet time and cost-efficient tool is needed to objectively evaluate CIPN. In this study we investigated the utility of gait parameters as such a measure of CIPN status that could complement clinical diagnoses made by physician assessment. Indeed, our preliminary findings support the potential of gait parameters as reliable markers to monitor the severity, progression and resolution of CIPN in cancer patients. Gait variable analyses across active CIPN patients, CIPN resolved patients and healthy controls Our findings show that gait parameters are significantly affected by CIPN status (Active CIPN, CIPN resolved, healthy controls) with effect sizes indicating varying levels of impact across different gait metrics (Table 3 ). The number of steps taken during walking (ε² = 0.755) and velocity (η²ₚ = 0.747) showed the largest effects, suggesting that neuropathy-induced sensory and motor impairments have a large influence on movement efficiency and functioning. The alteration in steppage may indicate a compensatory mechanism whereby patients take more steps to maintain balance and avoid falls. Ambulation time (η² = 0.614) also showed a strong effect, likely due to slower walking speed and cautious steppage, which lead to increased step duration and hesitation. Cadence (ε² = 0.450) and distance walked (ε² = 0.560) had relatively lower but still substantial effects (Table 3 ). This suggests that gait efficiency and step patterns were more significantly modified in active CIPN patients while their symptoms exerted a slightly smaller impact on the total distance walked. Active CIPN patients exhibited distinct gait patterns from resolved CIPN and healthy controls. We found that active CIPN patients had a significantly slower velocity (cm/s), shorter walking distance (cm), longer ambulation time (s) as compared to age-matched resolved and healthy controls (Table 3 , Figs. 3 – 5 ). Cadence (steps/min) was significantly lower in active CIPN participants as compared to healthy controls but not compared to CIPN resolved participants. Our findings confirm other studies on CIPN and its effect on functioning [ 35 , 44 , 56 ]. Similar observations have been made in diabetic peripheral neuropathic, Parkinson’s and alcohol-induced neuropathic patients [ 8 , 14 , 18 , 21 , 49 ]. The gait alterations in the active CIPN group are likely an adaptive response to reduced sensation and discomfort in the distal extremities. CIPN patients take slower steps, shorter strides, and spend prolonged periods in the standing phase to enhance stabilization which contribute to the increased stride time and reduced walking speed– a phenomenon shown to be correlated with cumulative doses of chemotherapy [ 40 , 56 , 58 ]. Slower voluntary stepping responses as a compensatory mechanism of sensorimotor deficits similar to that seen in patients with diabetic peripheral neuropathy (DPN) may also lead to velocity reduction in CIPN patients [ 37 , 45 ]. Psychological and central neurologic factors contributing to changes in gait patterns are also important. Fear of falling is associated with reduced walking speed as well as to the actual risk of falls and contributes to gait impairments [ 24 ]. In fact, CIPN patients are almost three times more likely to fall than non CIPN patients and this risk is correlated with severity of CIPN [ 28 , 59 ]. Particularly at risk are older patients or those with central nervous system (CNS) impairment, due to the CNS’ compensatory role in patients with peripheral nervous system deficiencies, further highlighting the need to screen for gait abnormalities to identify high-risk patients and facilitate early intervention [ 6 , 39 ]. Remarkably, CIPN resolved patients had no significant difference in velocity (cm/s), shorter walking distance (cm), shorter ambulation time (s), or cadence (steps/min) as compared to control patients, suggesting almost complete recovery in sensory and proprioceptive function (Table 3 , Figs. 2 – 5 ). The neuronal loss of the dorsal root ganglia (DRG) observed in CIPN is generally considered irreversible, which may explain why approximately a third of patients experience coasting symptoms following chemotherapy cessation. Impairments to sensory feedback primarily associated with the Aβ fibers in the DRG have shown to be a vulnerable target of platinum-based agents due to their lack of the blood-brain-barrier. Platinum agents accumulate in the DRG and form Pt-DNA adducts in the mitochondria, leading to neuronal apoptosis [ 9 ]. While the mechanisms are unclear, it has been suggested that oxaliplatin-induced damage, in roughly 80% of cases, is partially reversible, and 40% of patients achieve complete resolution 4 to 6 months following treatment cessation [ 5 , 11 , 36 ]. Disruption of microtubule dynamics and inflammation of mitochondria and the resultant damage of large, myelinated Aδ fibers and unmyelinated C fibers as well as motor fibers also contribute to CIPN [ 2 ]. However, peripheral nerves possess the capacity to partially regenerate after acute and chronic damage induced by microtubule-targeting chemotherapies and recover normal mitochondrial function and energy generation in neurons [ 57 ]. Unlike other gait parameters measured, the number of steps taken significantly differed among all three groups and between each group: healthy controls had fewer steps than both CIPN resolved and active CIPN groups, and CIPN resolved participants had fewer steps than active CIPN participants (Table 3 , Fig. 1 ). The increase in steppage in active CIPN patients may be due to persistence of learned behavior during patients’ symptomatic phase to increase stability and avoid falling. DPN patients have increased cadence but take shorter steps, necessitating a greater step count to maintain the same walking speed [ 43 ]. These patients have been reported to take 1.5 times more steps than healthy individuals to reach steady-state gait due to increase their stability and avoid the risk of falling [ 25 ]. Further research is needed to assess whether the prolonged increase in steps correlate with permanent neuroplastic changes or if this adaptation reversible via rehabilitative interventions. Correlation Between Gait Variables and TNAS Pain Scores Velocity (cm/s) and ambulation time (s) in active CIPN patients were strongly correlated with TNAS pain scores (Table 5 , Figs. 6 & 7 ). In our study, higher TNAS pain scores, indicating more intense chemotherapy-induced neuropathic pain, were associated with slower walking velocity and longer walking times ( p = 0.02 and 0.01, respectively). Similar findings have been previously reported. For example, cancer survivors with self-reported neuropathy exhibit increased step width variability and decreased step length variability compared to healthy controls [ 20 ]. These alterations in gait characteristics in neuropathic patients are linked to an increased risk of falls [ 20 ]. Similarly, higher Toronto Clinical Neuropathy Scores (TCNS), a composite clinical tool which incorporates both subjective symptom reporting and objective neurological assessments, was associated with decreased step length, stride length, and foot height in gait analysis in DPN patients [ 49 ]. Patients with self-reported polyneuropathy also demonstrated altered gait characteristics, such as slower walking speed and cadence, as well as increased errors during tandem walking [ 14 ]. Likewise, we demonstrate that gait parameters can serve as an objective and practical measure of functional capability and clinical severity in CIPN. Correlation between Gait Variables and PROMIS® 29 + 2 Profile v2.1 (PROPr) domains To our knowledge, this is the first study to explore the relationship between multiple gait variables and PROPr domains. PROPr is a valid tool to assess patient health-related QOL domains in the clinical and research settings [ 10 , 15 , 50 ]. Further, PROMIS scores can distinguish populations with and without motor impairment [ 31 ]. Our findings demonstrate that patients experiencing greater levels of pain interference and intensity exhibit worsened gait characteristics. In fact, we found a significant correlation between the PROPr pain domains and each of the five gait variables (distance (cm), velocity (cm/s), cadence (steps/min), number of steps, ambulation time (s)) in this study (Table 6 , Fig. 8 ). Individuals with greater pain scores on the PROPr tend to take walk slower and have increased walking times. We also found a significant association between physical function and the gait variables velocity and ambulation time. Here, we found that worse physical function was correlated with impaired gait capabilities (Table 6 , Fig. 8 ). Similar to our findings, a previous study on individuals with cerebral palsy has shown that slower walking speeds were significantly correlated with physical function and pain interference [ 33 ]. With the association between gait variables and the validated PROPr domains, we show that gait metrics can reveal pain-related functional impairments in patients with CIPN. Limitations This pilot study has several limitations. While multiple gait parameter measurements were obtained, the sample size was small and heterogeneous and the three groups were matched in terms of age, but not any other variables such as race or gender. A larger and more diverse sample size is needed to determine the practicability of establishing gait metrics as a clinical tool to determine CIPN severity. The “healthy control” group was considered CIPN-free; however, these participants may have had other underlying pathologies contributing to gait abnormalities which we did not account for in this study. Additionally, differences in the chemotherapy agents may be an underlying confounder. Due to the cross-sectional nature of this study, we were not able to assess the changes in gait patterns during recovery from CIPN. Conclusion The current pilot study serves as an initial attempt to garner evidence for the utility of gait measurements as a functional test to monitor gait changes as it pertains to pain changes in an outpatient setting. Indeed, the findings underscore the potential of gait parameters as an objective diagnostic tool that is accurate, non-invasive, cost and time effective. However, given the limitations, future studies should assess the feasibility and reliability of gait metrics usage in the clinical diagnosis of CIPN by incorporating a larger and more diverse sample. In addition, a larger cohort of patients longitudinally to evaluate how gait parameters change during CIPN recovery. Declarations Author Contributions Serena Kim : Writing – Original Draft Preparation, Formal Analysis, Visualization. Patrick Dougherty : Conceptualization, Writing – Review & Editing Salahadin Abdi : Conceptualization, Writing – Review & Editing Saba Javed : Conceptualization, Investigation, Methodology, Resources, Supervision, Writing – Review & Editing. Ethics Declaration This research was conducted in accordance with the ethical standards set forth in the Declaration of Helsinki for research involving human participants. This study was approved by the MD Anderson Institutional Review Board Protocol 2024-0368. Disclosures This research did not receive any funding. The authors have no conflicts of interest to declare for this work. Data Availability The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Acknowledgements The authors thank all patients and healthy controls for their participation in this study. We thank Dr. Marina Masciale for her valuable feedback and guidance in preparing the manuscript. 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Mapping chemotherapy-induced peripheral neuropathy phenotype and health-related quality of life in patients with cancer through exploratory analysis of multimodal assessment data. Support Care Cancer 2022;30:4007–4017. doi:10.1007/s00520-022-06821-0. Winters-Stone KM, Horak F, Jacobs PG, Trubowitz P, Dieckmann NF, Stoyles S, Faithfull S. Falls, Functioning, and Disability Among Women With Persistent Symptoms of Chemotherapy-Induced Peripheral Neuropathy. J Clin Oncol Off J Am Soc Clin Oncol 2017;35:2604–2612. Wozniak KM, Vornov JJ, Wu Y, Liu Y, Carozzi VA, Rodriguez-Menendez V, Ballarini E, Alberti P, Pozzi E, Semperboni S, Cook BM, Littlefield BA, Nomoto K, Condon K, Eckley S, DesJardins C, Wilson L, Jordan MA, Feinstein SC, Cavaletti G, Polydefkis M, Slusher BS. Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery. Cancer Res 2018;78:817–829. doi:10.1158/0008-5472.CAN-17-1467. Wright MJ, Twose DM, Gorter JW. Gait characteristics of children and youth with chemotherapy induced peripheral neuropathy following treatment for acute lymphoblastic leukemia. Gait Posture 2017;58:139–145. doi:10.1016/j.gaitpost.2017.05.004. Zahiri M, Chen KM, Zhou H, Nguyen H, Workeneh BT, Yellapragada SV, Sada YH, Schwenk M, Najafi B. Using wearables to screen motor performance deterioration because of cancer and chemotherapy-induced peripheral neuropathy (CIPN) in adults - Toward an early diagnosis of CIPN. J Geriatr Oncol 2019;10:960–967. doi:10.1016/j.jgo.2019.01.010. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 03 Mar, 2026 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Revision requested 22 Dec, 2025 Reviews received at journal 21 Dec, 2025 Reviews received at journal 09 Dec, 2025 Reviewers agreed at journal 07 Dec, 2025 Reviewers agreed at journal 16 Nov, 2025 Reviewers agreed at journal 05 Jul, 2025 Reviewers invited by journal 24 Jun, 2025 Editor assigned by journal 24 Jun, 2025 Submission checks completed at journal 23 May, 2025 First submitted to journal 14 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6666978","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":476331891,"identity":"3ba12730-cbd0-4940-9772-87c8979bc905","order_by":0,"name":"Serena Jiyeon Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYFCCYwwHGHhsGIAkgwQJWmTSSNLCBsQ2h0nQIt94LPHQjZzz0XzHzx688XFPnZw5A/Oxj1/waDE4cOzA4Zwzt3NnnslLtpzx7LCxZQNb8mwZfFoYjjcczu25nbvhQI6ZNM+BA4kbDvAYM+NzonwDSMu/c7kbzr8xk/5zoI6wFgaww3gO5G64AbSF4QAzWAvjB/x+SQBqSc6deeONsWXPgcPGBofZkpnxWSI/45jx5xweu9y+8zmGN34cqJMzON58mPEHPj0SB9BFgFYw8+DTwt+ARRC/LaNgFIyCUTDSAADBb1ve/02IowAAAABJRU5ErkJggg==","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":true,"prefix":"","firstName":"Serena","middleName":"Jiyeon","lastName":"Kim","suffix":""},{"id":476331892,"identity":"b1ad6364-9b7e-44fb-893d-0c51acdae50e","order_by":1,"name":"Patrick Dougherty","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Dougherty","suffix":""},{"id":476331893,"identity":"97a9b442-dc43-47a8-aa40-4fa77a81ab37","order_by":2,"name":"Salahadin Abdi","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Salahadin","middleName":"","lastName":"Abdi","suffix":""},{"id":476331894,"identity":"48dabe28-fda6-4ea4-8e1f-88bc8dec6824","order_by":3,"name":"Saba Javed","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Saba","middleName":"","lastName":"Javed","suffix":""}],"badges":[],"createdAt":"2025-05-14 19:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6666978/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6666978/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00520-026-10507-2","type":"published","date":"2026-03-03T15:58:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85735985,"identity":"e6fd1ed2-fa9a-41ec-924c-cf2cd531c7b7","added_by":"auto","created_at":"2025-07-01 08:04:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":89976,"visible":true,"origin":"","legend":"\u003cp\u003eBox plot showing the number of steps taken during walking across participant groups. Line at mean. Error bars represent standard deviation. Healthy Control vs. CIPN Resolved: W = 3.96, \u003cem\u003ep\u003c/em\u003e = 0.014; Healthy Control vs. Active CIPN: W = 5.12, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; CIPN Resolved vs. Active CIPN: W = 4.50, \u003cem\u003ep\u003c/em\u003e= 0.004\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/75d344ba7c2d095ab6d1780c.png"},{"id":85737362,"identity":"e338cde5-741c-4aaa-9470-c353753bd858","added_by":"auto","created_at":"2025-07-01 08:12:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":92108,"visible":true,"origin":"","legend":"\u003cp\u003eBox plot showing cadence during walking across participant groups. Line at mean. Error bars represent standard deviation. Healthy Control vs. CIPN Resolved: W = 3.06, \u003cem\u003ep\u003c/em\u003e = 0.077; Healthy Control vs. Active CIPN: W = 4.25, \u003cem\u003ep\u003c/em\u003e = 0.007; CIPN Resolved vs. Active CIPN: W = 2.81, \u003cem\u003ep\u003c/em\u003e= 0.115\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/419ecafa64783dea1cf8e3fb.png"},{"id":85735990,"identity":"9ef08ef4-a51e-4559-bcdd-1a058435d5f2","added_by":"auto","created_at":"2025-07-01 08:04:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":90968,"visible":true,"origin":"","legend":"\u003cp\u003eBox plot showing the ambulation time during walking across participant groups. Line at mean. Error bars represent standard deviation. CIPN Resolved vs. Active CIPN: t = -10.64, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; Healthy Control vs. Active CIPN: t = -11.24, \u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001; Healthy Control vs. CIPN Resolved: t = -0.60, \u003cem\u003ep\u003c/em\u003e = 0.819\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/61b544c12d832e6523510276.png"},{"id":85737365,"identity":"3949f77f-31c3-449a-9491-c0d1a9ec1f21","added_by":"auto","created_at":"2025-07-01 08:12:54","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":90629,"visible":true,"origin":"","legend":"\u003cp\u003eBox plot showing distance walked during walking across participant groups. Line at mean. Error bars represent standard deviation. CIPN Resolved vs. Active CIPN: W = -4.37, \u003cem\u003ep\u003c/em\u003e = 0.006; Healthy Control vs. Active CIPN: W= -4.72, \u003cem\u003ep\u003c/em\u003e = 0.002; Healthy Control vs. CIPN Resolved: W = -1.46, \u003cem\u003ep\u003c/em\u003e= 0.558\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/50aab02a43423fd168ff034e.png"},{"id":85735992,"identity":"7d14be4b-8b8d-41ea-9267-ff59831f7264","added_by":"auto","created_at":"2025-07-01 08:04:54","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":91743,"visible":true,"origin":"","legend":"\u003cp\u003eBox plot showing the velocity during walking across participant groups. Line at mean. Error bars represent standard deviation. CIPN Resolved vs. Active CIPN: t = 6.88, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; Healthy Control vs. Active CIPN: t = 7.35, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; Healthy Control vs. CIPN Resolved: t = 0.47, \u003cem\u003ep\u003c/em\u003e= 0.644\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/fe7b8baf6201eb6ea1c0efc2.png"},{"id":85738879,"identity":"028bd4dc-4489-4bec-aafd-a193f10f0118","added_by":"auto","created_at":"2025-07-01 08:28:54","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":165013,"visible":true,"origin":"","legend":"\u003cp\u003eRegression plot showing the relationship between pain scores (TNAS) and CIPN velocity (cm/s). Blue regression line represents the predicted relationship between pain and walking velocity. Shaded area indicates the 95% confidence interval. Pearson’s r = −0.737, \u003cem\u003ep\u003c/em\u003e = 0.023.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/38488657e92dd37c9db3bb3e.png"},{"id":85736008,"identity":"f8390cdd-6051-46f7-9f34-eaf680a34f74","added_by":"auto","created_at":"2025-07-01 08:04:54","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":164475,"visible":true,"origin":"","legend":"\u003cp\u003eRegression plot showing the relationship between pain scores (TNAS) and ambulation time (s). The blue regression line represents the predicted relationship between pain and walking time, with the shaded area indicating the 95% confidence interval. Pearson’s r = 0.788, \u003cem\u003ep\u003c/em\u003e = 0.012.\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/3fb1f4c26a599bfb6065700a.png"},{"id":85736004,"identity":"ad1e16f7-5435-4633-94b8-0745fce830cb","added_by":"auto","created_at":"2025-07-01 08:04:54","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":597453,"visible":true,"origin":"","legend":"\u003cp\u003eRegression plot showing the relationship between PROPr domains (pain intensity, pain interference, physical function) and gait variables (distance (cm), velocity (cm/s), cadence (steps/min), number of steps, ambulation time (s)). The blue regression line represents the predicted relationship between PROPr 29 domains and gait variables with the shaded area indicating the 95% confidence interval.\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/5fac2832c98cd2ccaf066918.png"},{"id":104250663,"identity":"e50b072f-abba-4b53-b6fa-08788b3153c0","added_by":"auto","created_at":"2026-03-09 16:04:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2540889,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6666978/v1/fdf8bed8-df01-495d-81db-19f5bea12b6f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gait as a Quantitative Indicator of the Severity of Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and prevalent side effect of neoplastic agents [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. CIPN may occur during neurotoxic chemotherapy treatment or following its termination, i.e., \u0026ldquo;coasting,\u0026rdquo; a phenomenon associated with agents such as cisplatin and oxaliplatin [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The incidence of CIPN is agent-dependent and is reported to range between 11\u0026ndash;100%, with approximately a third of patients experiencing \u0026ldquo;coasting\u0026rdquo; symptoms lasting 6 months or more after chemotherapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCIPN predominantly involves sensory neurons in a length-and-dose-dependent manner; motor and autonomic neural deficits are less common and usually observed at higher chemotherapy dosages. CIPN symptoms typically manifest in a symmetrical stocking-glove distribution with pain, paresthesias, dysesthesias, decreased sensitivity to vibration, and impaired proprioception [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In advanced stages, CIPN affects motor function, balance, and strength in distal extremities [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Due to such side effects CIPN leads to altered psychophysical characteristics such as gait abnormalities, impaired balance, postural instability and increased risk of falls [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. Consequently, CIPN interferes with patients\u0026rsquo; daily functioning and diminishes their quality of life and necessitates dose reduction or cessation of chemotherapy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, there is a lack of an objective and standardized method to measure CIPN severity. Patient-reported outcome (PRO) measures, such as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-CIPN20), are widely used to evaluate the severity and progression of CIPN. However, self-reported tools of CIPN are prone to inaccuracies due to their subjective nature and variability in symptom reporting, influenced by individual adaptation to symptoms and underreporting of symptoms due to distrust or frustration toward healthcare providers [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. While the EORTC-CIPN20 demonstrates good interrater and test-retest reliability, it suffers from variability in patient interpretation of test items, conceptual misalignment, response bias and discrepancies from clinical evaluations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, placebo and nocebo effects have been reported in diabetic peripheral neuropathy (DPN) and fibromyalgia patients in which patients report moderate pain relief in randomized control trials after receiving oral placebo medications. More than half of the patients in the placebo arm also reported adverse effects [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Placebo effects accounted for up to 45% of active drug responses in fibromyalgia and 62% in DPN trials with a significant positive correlation between placebo and drug effects [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Hence, placebo and nocebo responses may further complicate assessing the effectiveness of treatment options for CIPN.\u003c/p\u003e \u003cp\u003eAs such, a reliable tool is essential for objectively assessing CIPN severity to best guide practitioners in determining optimal interventions and symptom relief strategies. The goal of this pilot study was to preliminarily test the premise that gait parameters would provide such a metric and to inform the design of future investigations on its clinical usage. Further assessment with a larger sample population is necessary to confirm the feasibility and reliability in clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eRecruitment\u003c/h2\u003e\n \u003cp\u003eThis prospective case series and pilot investigation was approved by MD Anderson Institutional Review Board Protocol 2024\u0026thinsp;\u0026minus;\u0026thinsp;0368. A total of 27 patients between the ages 45 and 72 seen at a pain management clinic at a large cancer center in Houston, Texas between Jan. 1st, 2024 and Dec 31st, 2024 were selected for this study. CIPN status of participants was determined by clinical diagnosis and each group (CIPN active, CIPN resolved, and healthy controls) was composed of 9 patients. CIPN resolution was determined by the improvement of clinical symptoms of CIPN, such as \u0026quot;burning, tingling, numbness, and cold sensations,\u0026quot; until the symptoms fully resolved. The inclusion and exclusion criteria are listed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Informed consent was received from all participants.\u003c/p\u003e\n \u003cp\u003eThe three groups were age-matched. In addition to age, other demographic data including gender and race were collected. The data collected for this study are presented in summative form. Individual data points are not publicly available to maintain patient confidentiality. They may be obtained by contacting the corresponding author with a reasonable request.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of Inclusion and Exclusion Criteria\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInclusion Criteria\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExclusion Criteria\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eActive CIPN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e● Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years and \u0026le;\u0026thinsp;85 years\u003c/p\u003e\n \u003cp\u003e● Pain score\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;5 on a scale of 0 to 10\u003c/p\u003e\n \u003cp\u003e● Patients diagnosed with painful CIPN of lower extremity due to either vinca alkaloids or platinum-based compounds\u003c/p\u003e\n \u003cp\u003e● CIPN symptoms present for \u0026ge; 6 months;\u003c/p\u003e\n \u003cp\u003e● Not currently undergoing chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e● Patients with cognitive dysfunction or pre-existing gait dysfunction due to underlying neurologic dysfunction\u003c/p\u003e\n \u003cp\u003e● Patient with recent history (\u0026lt;\u0026thinsp;6 months) of drug or alcohol abuse\u003c/p\u003e\n \u003cp\u003e● Patients with open skin lesion or undergoing antibiotic therapy for local or systemic infection\u003c/p\u003e\n \u003cp\u003e● Patients with painful diabetic peripheral neuropathy or other preexisting peripheral neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCIPN resolved\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e● Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years and \u0026le;\u0026thinsp;85 years\u003c/p\u003e\n \u003cp\u003e● Patients with prior clinically diagnosed history of CIPN of lower extremity, now resolved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy Control\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e● Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years and \u0026le;\u0026thinsp;85 years\u003c/p\u003e\n \u003cp\u003e● Patients with no prior history of chemotherapy or any form of neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eGait Assessment\u003c/h3\u003e\n\u003cp\u003eGait assessment was conducted using the GAITRite\u0026reg; Walkway (GAITRite machine, CIR Systems, Sparta, NJ), a reliable tool to detect kinetic forces, time sensor activation, and measure relative distances between sensors [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. Quantitative gait parameters including distance, ambulation time, velocity, number of steps, and cadence were recorded [\u003cspan class=\"CitationRef\"\u003e54\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eTreatment-Induced Neuropathy Assessment Scale (TNAS) Scores\u003c/h3\u003e\n\u003cp\u003eThe TNAS v3.0 is a valid and reliable patient-reported outcome measure for assessing treatment-induced peripheral neuropathy (TIPN) [\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e]. The TNAS evaluates multiple domains: pain, tingling, numbness, hot/burning sensations, coldness, difficulty using fingers, balance/fall risk, walking difficulties, and sleep disturbances. TNAS pain scores were used to analyze their relationship with gait variables (distance, ambulation time, velocity, number of steps, and cadence).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePROMIS\u0026reg; 29+2 Profile v2.1 (PROPr)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePROPr is a patient-reported outcome measure of health-based quality of life (QOL) assessed over the following 7 domains: physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain interference. It incorporates the 29 items from the PROMIS-29 Profile v2.1 and two additional items for a more comprehensive coverage of health-related QOL.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses in this study were generated using Jamovi, version 2.6.23 (The Jamovi Project, Sydney, Australia). Data visualization was conducted using R (version 4.4.2; R Core Team, 2023) within RStudio (Posit, 2023).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDemographics\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA Kruskal-Wallis test was run to compare the age among the CIPN active, CIPN resolved, and healthy control groups. Fisher\u0026rsquo;s exact test was used to assess race distribution among the groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGait variable analyses\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Shapiro-Wilk test was applied to assess normality and the Levene\u0026rsquo;s test to assess homogeneity of variances for all data: demographics, number of steps, cadence, ambulation time, distance and velocity. Kruskal Wallis was used to compare among the active CIPN, CIPN resolved, and healthy control groups.\u003c/p\u003e\n\u003cp\u003eAs previous literature indicates that age and gender may have a modulatory role in gait characteristics, a linear regression was performed to determine any significant relationship between the variables and gait parameters that were measured in this study [7,27,46,52]. If there was a significant relationship, an analysis of covariance (ANCOVA) was used to compare the gait variable across CIPN active, CIPN resolved, and healthy control groups. If the homogeneity of regression slopes was violated, a general linear model was used.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIf there was no significant relationship with age and gender and the assumptions of normality were met but not the homogeneity of variances, a Welch\u0026rsquo;s test with the Games-Howell Post-Hoc test was conducted. If neither assumption were met, a Kruskal-Wallis test with the Dwass-Steel-Critchlow-Fligner pairwise comparison was conducted. An alpha value of \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05 was defined as statistically significant. Effect sizes were also calculated to provide additional context for the magnitude of group differences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCorrelation Between Gait Variables and TNAS Pain Scores\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs the variables were normally distributed, Pearson\u0026rsquo;s correlation was used to assess the relationship between gait variables and TNAS pain scores in active CIPN patients. An alpha value of \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05 was defined as statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCorrelation between Gait Variables and PROMIS\u0026reg; 29+2 Profile v2.1 (PROPr) domains\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData from all three groups (active CIPN, CIPN resolved, and healthy control) were pooled to correlate gait variables and PROPr domains. This approach allows for determining whether gait variables can serve as an objective measure across all severities/status of CIPN. \u0026nbsp;For normally distributed data, Pearson\u0026rsquo;s correlation was used to assess the relationship between all the gait variables and the following PROMIS\u0026reg; 29+2 Profile v2.1 (PROPr) domains: pain intensity, pain interference, physical function. For non-normally distributed data, Spearman\u0026apos;s correlation was used. An alpha value of \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05 was defined as statistically significant.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003cbr\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic Information of Participants (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCIPN active (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCIPN resolved (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHealthy Controls (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (males/females)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.861\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfrican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaucasian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (55.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (22.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (22.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs the number of male and female participants in each study group was equal, there was no statistical difference between the distribution of males and females (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.00) among the groups. The age distribution was also similar between each group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.972) with the mean age of approximately 60 years old for each group. Finally, there was no significant difference in the distribution of race (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.673), which was considered as a social and cultural construct for this study (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of gait parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGait variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCIPN active (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCIPN resolved (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eHealthy Controls (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eEffect size\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eM\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eM\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eM\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eSD\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of steps\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.17*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.56*\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05 \u003csup\u003eH\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadence (steps / min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e204.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e75.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e58.72*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003csup\u003eH\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmbulation time (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.22*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.11*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.614\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003eFa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistance (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e484.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e510.56*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e514.44*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003eH\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVelocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e65.86*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e66.67*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e16.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.747\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003eFg\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cb\u003eNote\u003c/b\u003e: \u003cem\u003eM\u003c/em\u003e indicates mean. * indicates a significant difference with the CIPN active group; \u003csup\u003e+\u003c/sup\u003e indicates a significant difference with the CIPN resolved group. \u003csup\u003eH\u003c/sup\u003e represents Kruskal-Wallis H-test; \u003csup\u003eFa\u003c/sup\u003e represents ANCOVA F-test; \u003csup\u003eFg\u003c/sup\u003e represents general linear model F-test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eNUMBER OF STEPS\u003c/h2\u003e \u003cp\u003eThe healthy control group took significantly fewer steps (7.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73) to complete the 16-foot mat twice than both the CIPN resolved (10.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24) and active CIPN groups (44.11\u0026thinsp;\u0026plusmn;\u0026thinsp;20.68). The CIPN resolved group took significantly fewer steps compared to the active CIPN group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eCADENCE\u003c/h2\u003e \u003cp\u003eThe CIPN active group had a significantly greater cadence (steps / minute) than the healthy controls. There was no significant difference in cadence between the healthy control and CIPN resolved participants or between CIPN resolved and active CIPN participants (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eAMBULATION TIME\u003c/h2\u003e \u003cp\u003eThe active CIPN group exhibited a significantly longer ambulation time (13.11\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03) than the CIPN resolved (8.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11) and healthy control (8.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.76) group. There was no significant difference in ambulation time between the healthy control and CIPN resolved groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eDISTANCE\u003c/h2\u003e \u003cp\u003eThe active CIPN group travelled a significantly lesser distance (484.89\u0026thinsp;\u0026plusmn;\u0026thinsp;19.91) than the CIPN resolved group (510.56\u0026thinsp;\u0026plusmn;\u0026thinsp;8.35) and healthy control (514.44\u0026thinsp;\u0026plusmn;\u0026thinsp;7.14). There was no significant difference in walking distance between CIPN resolved and healthy control groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eVELOCITY\u003c/h2\u003e \u003cp\u003eThe active CIPN group displayed a significantly slower velocity (37.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6.04) than the healthy controls (66.67\u0026thinsp;\u0026plusmn;\u0026thinsp;16.95) and CIPN resolved (65.86\u0026thinsp;\u0026plusmn;\u0026thinsp;16.67) group. However, there was no significant difference in velocity between healthy controls and those with resolved CIPN (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment-Induced Neuropathy Assessment Scale scores in Active CIPN patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNAS category\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumbness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTingling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWalking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHot/burning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColdness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifficulty using fingers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBalance/fall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between TNAS Pain Scores and Gait Variables in Active CIPN patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGait variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e (df\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of steps\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.918\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadence (steps / min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.602\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmbulation time (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.788\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.012*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistance (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.428\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVelocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.737\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.023*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eTNAS Pain Scores vs. Velocity (cm/s) in Active CIPN patients\u003c/h2\u003e \u003cp\u003eThe average TNAS scores for active CIPN patients ranged between 6.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23 (numbness) and 8.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97 (sleep). The average pain score was 7.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13 (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). There was a significant negative correlation between TNAS pain scores and walking velocity in Active CIPN patients (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.737, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023), indicating that higher pain scores were associated with slower walking speed (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eTNAS Pain Scores vs. Ambulation Time (s) in Active CIPN Patients\u003c/h2\u003e \u003cp\u003eThere was a significant positive correlation between TNAS pain scores and ambulation time in Active CIPN patients (r\u0026thinsp;=\u0026thinsp;0.788, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), indicating that higher pain scores were associated with longer walking times (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between PROPr domains and Gait Variables in active CIPN patients, CIPN resolved patients, and healthy controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGait variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePain Intensity (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePain Interference (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003ePhysical Function (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ecorrelation*\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ecorrelation\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ecorrelation\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of steps\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadence (steps / min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmbulation time (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eρ\u003c/em\u003e = -0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistance (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVelocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*unless otherwise indicated with \u0026ldquo;\u003cem\u003eρ\u003c/em\u003e\u0026rdquo; which represents Spearman\u0026rsquo;s correlation, all other correlation values represent \u0026ldquo;\u003cem\u003er\u003c/em\u003e\u0026rdquo; from Pearson\u0026rsquo;s correlation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003ePain intensity\u003c/h2\u003e \u003cp\u003eAmbulation time (\u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.82, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01 was significantly positively correlated with pain intensity, indicating that individuals who experience greater pain walk for a longer period.\u003c/p\u003e \u003cp\u003eVelocity (\u003cem\u003er\u003c/em\u003e = -0.73, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) was significantly negatively correlated with pain intensity, suggesting that individuals who experience greater pain walk slower (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003ePain Interference\u003c/h2\u003e \u003cp\u003eAmbulation time (\u003cem\u003eρ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.80, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) was significantly positively correlated with pain interference, which aligns with the findings for pain intensity. Velocity (\u003cem\u003er\u003c/em\u003e = -0.80, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) had significantly negative correlations with pain interference (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003ePhysical Function\u003c/h2\u003e \u003cp\u003eAmbulation time (\u003cem\u003eρ\u003c/em\u003e = -0.82, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) was negatively correlated with physical function, suggesting that individuals with better physical functioning have better gait characteristics such as walking for shorter periods.\u003c/p\u003e \u003cp\u003eVelocity (\u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.77, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) was positively correlated with physical function, indicating that individuals with better physical function walk faster (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eA more reliable yet time and cost-efficient tool is needed to objectively evaluate CIPN. In this study we investigated the utility of gait parameters as such a measure of CIPN status that could complement clinical diagnoses made by physician assessment. Indeed, our preliminary findings support the potential of gait parameters as reliable markers to monitor the severity, progression and resolution of CIPN in cancer patients.\u003c/p\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eGait variable analyses across active CIPN patients, CIPN resolved patients and healthy controls\u003c/h2\u003e \u003cp\u003eOur findings show that gait parameters are significantly affected by CIPN status (Active CIPN, CIPN resolved, healthy controls) with effect sizes indicating varying levels of impact across different gait metrics (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The number of steps taken during walking (ε\u0026sup2; = 0.755) and velocity (η\u0026sup2;ₚ = 0.747) showed the largest effects, suggesting that neuropathy-induced sensory and motor impairments have a large influence on movement efficiency and functioning. The alteration in steppage may indicate a compensatory mechanism whereby patients take more steps to maintain balance and avoid falls. Ambulation time (η\u0026sup2; = 0.614) also showed a strong effect, likely due to slower walking speed and cautious steppage, which lead to increased step duration and hesitation. Cadence (ε\u0026sup2; = 0.450) and distance walked (ε\u0026sup2; = 0.560) had relatively lower but still substantial effects (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This suggests that gait efficiency and step patterns were more significantly modified in active CIPN patients while their symptoms exerted a slightly smaller impact on the total distance walked.\u003c/p\u003e \u003cp\u003eActive CIPN patients exhibited distinct gait patterns from resolved CIPN and healthy controls. We found that active CIPN patients had a significantly slower velocity (cm/s), shorter walking distance (cm), longer ambulation time (s) as compared to age-matched resolved and healthy controls (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Cadence (steps/min) was significantly lower in active CIPN participants as compared to healthy controls but not compared to CIPN resolved participants. Our findings confirm other studies on CIPN and its effect on functioning [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. Similar observations have been made in diabetic peripheral neuropathic, Parkinson\u0026rsquo;s and alcohol-induced neuropathic patients [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe gait alterations in the active CIPN group are likely an adaptive response to reduced sensation and discomfort in the distal extremities. CIPN patients take slower steps, shorter strides, and spend prolonged periods in the standing phase to enhance stabilization which contribute to the increased stride time and reduced walking speed\u0026ndash; a phenomenon shown to be correlated with cumulative doses of chemotherapy [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Slower voluntary stepping responses as a compensatory mechanism of sensorimotor deficits similar to that seen in patients with diabetic peripheral neuropathy (DPN) may also lead to velocity reduction in CIPN patients [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Psychological and central neurologic factors contributing to changes in gait patterns are also important. Fear of falling is associated with reduced walking speed as well as to the actual risk of falls and contributes to gait impairments [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In fact, CIPN patients are almost three times more likely to fall than non CIPN patients and this risk is correlated with severity of CIPN [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Particularly at risk are older patients or those with central nervous system (CNS) impairment, due to the CNS\u0026rsquo; compensatory role in patients with peripheral nervous system deficiencies, further highlighting the need to screen for gait abnormalities to identify high-risk patients and facilitate early intervention [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRemarkably, CIPN resolved patients had no significant difference in velocity (cm/s), shorter walking distance (cm), shorter ambulation time (s), or cadence (steps/min) as compared to control patients, suggesting almost complete recovery in sensory and proprioceptive function (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The neuronal loss of the dorsal root ganglia (DRG) observed in CIPN is generally considered irreversible, which may explain why approximately a third of patients experience coasting symptoms following chemotherapy cessation. Impairments to sensory feedback primarily associated with the Aβ fibers in the DRG have shown to be a vulnerable target of platinum-based agents due to their lack of the blood-brain-barrier. Platinum agents accumulate in the DRG and form Pt-DNA adducts in the mitochondria, leading to neuronal apoptosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. While the mechanisms are unclear, it has been suggested that oxaliplatin-induced damage, in roughly 80% of cases, is partially reversible, and 40% of patients achieve complete resolution 4 to 6 months following treatment cessation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Disruption of microtubule dynamics and inflammation of mitochondria and the resultant damage of large, myelinated Aδ fibers and unmyelinated C fibers as well as motor fibers also contribute to CIPN [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, peripheral nerves possess the capacity to partially regenerate after acute and chronic damage induced by microtubule-targeting chemotherapies and recover normal mitochondrial function and energy generation in neurons [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUnlike other gait parameters measured, the number of steps taken significantly differed among all three groups and between each group: healthy controls had fewer steps than both CIPN resolved and active CIPN groups, and CIPN resolved participants had fewer steps than active CIPN participants (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The increase in steppage in active CIPN patients may be due to persistence of learned behavior during patients\u0026rsquo; symptomatic phase to increase stability and avoid falling. DPN patients have increased cadence but take shorter steps, necessitating a greater step count to maintain the same walking speed [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. These patients have been reported to take 1.5 times more steps than healthy individuals to reach steady-state gait due to increase their stability and avoid the risk of falling [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Further research is needed to assess whether the prolonged increase in steps correlate with permanent neuroplastic changes or if this adaptation reversible via rehabilitative interventions.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eCorrelation Between Gait Variables and TNAS Pain Scores\u003c/h2\u003e \u003cp\u003eVelocity (cm/s) and ambulation time (s) in active CIPN patients were strongly correlated with TNAS pain scores (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Figs.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e \u0026amp; \u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). In our study, higher TNAS pain scores, indicating more intense chemotherapy-induced neuropathic pain, were associated with slower walking velocity and longer walking times (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02 and 0.01, respectively). Similar findings have been previously reported. For example, cancer survivors with self-reported neuropathy exhibit increased step width variability and decreased step length variability compared to healthy controls [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These alterations in gait characteristics in neuropathic patients are linked to an increased risk of falls [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Similarly, higher Toronto Clinical Neuropathy Scores (TCNS), a composite clinical tool which incorporates both subjective symptom reporting and objective neurological assessments, was associated with decreased step length, stride length, and foot height in gait analysis in DPN patients [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Patients with self-reported polyneuropathy also demonstrated altered gait characteristics, such as slower walking speed and cadence, as well as increased errors during tandem walking [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Likewise, we demonstrate that gait parameters can serve as an objective and practical measure of functional capability and clinical severity in CIPN.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eCorrelation between Gait Variables and PROMIS\u0026reg; 29\u0026thinsp;+\u0026thinsp;2 Profile v2.1 (PROPr) domains\u003c/h2\u003e \u003cp\u003eTo our knowledge, this is the first study to explore the relationship between multiple gait variables and PROPr domains. PROPr is a valid tool to assess patient health-related QOL domains in the clinical and research settings [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Further, PROMIS scores can distinguish populations with and without motor impairment [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Our findings demonstrate that patients experiencing greater levels of pain interference and intensity exhibit worsened gait characteristics. In fact, we found a significant correlation between the PROPr pain domains and each of the five gait variables (distance (cm), velocity (cm/s), cadence (steps/min), number of steps, ambulation time (s)) in this study (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Individuals with greater pain scores on the PROPr tend to take walk slower and have increased walking times. We also found a significant association between physical function and the gait variables velocity and ambulation time. Here, we found that worse physical function was correlated with impaired gait capabilities (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Similar to our findings, a previous study on individuals with cerebral palsy has shown that slower walking speeds were significantly correlated with physical function and pain interference [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. With the association between gait variables and the validated PROPr domains, we show that gait metrics can reveal pain-related functional impairments in patients with CIPN.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis pilot study has several limitations. While multiple gait parameter measurements were obtained, the sample size was small and heterogeneous and the three groups were matched in terms of age, but not any other variables such as race or gender. A larger and more diverse sample size is needed to determine the practicability of establishing gait metrics as a clinical tool to determine CIPN severity. The \u0026ldquo;healthy control\u0026rdquo; group was considered CIPN-free; however, these participants may have had other underlying pathologies contributing to gait abnormalities which we did not account for in this study. Additionally, differences in the chemotherapy agents may be an underlying confounder. Due to the cross-sectional nature of this study, we were not able to assess the changes in gait patterns during recovery from CIPN.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe current pilot study serves as an initial attempt to garner evidence for the utility of gait measurements as a functional test to monitor gait changes as it pertains to pain changes in an outpatient setting. Indeed, the findings underscore the potential of gait parameters as an objective diagnostic tool that is accurate, non-invasive, cost and time effective. However, given the limitations, future studies should assess the feasibility and reliability of gait metrics usage in the clinical diagnosis of CIPN by incorporating a larger and more diverse sample. In addition, a larger cohort of patients longitudinally to evaluate how gait parameters change during CIPN recovery.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerena Kim\u003c/strong\u003e: Writing – Original Draft Preparation, Formal Analysis, Visualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatrick Dougherty\u003c/strong\u003e: Conceptualization, Writing – Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSalahadin Abdi\u003c/strong\u003e: Conceptualization, Writing – Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSaba Javed\u003c/strong\u003e: Conceptualization, Investigation, Methodology, Resources, Supervision, Writing – Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was conducted in accordance with the ethical standards set forth in the Declaration of Helsinki for research involving human participants. This study\u0026nbsp;was approved by the MD Anderson Institutional Review Board Protocol 2024-0368.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any funding.\u0026nbsp;The authors have no conflicts of interest to declare for this work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all patients and healthy controls for their participation in this study. We thank Dr. Marina Masciale for her valuable feedback and guidance in preparing the manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlberti P, Rossi E, Cornblath DR, Merkies ISJ, Postma TJ, Frigeni B, Bruna J, Velasco R, Argyriou AA, Kalofonos HP, Psimaras D, Ricard D, Pace A, Gali\u0026egrave; E, Briani C, Dalla Torre C, Faber CG, Lalisang RI, Boogerd W, Brandsma D, Koeppen S, Hense J, Storey D, Kerrigan S, Schenone A, Fabbri S, Valsecchi MG, Cavaletti G, Cavaletti G, Cornblath DR, Merkies ISJ, Postma TJ, Valsecchi MG, Galimberti S, Rossi E, Cavaletti G, Frigeni B, Lanzani F, Mattavelli L, Piatti ML, Alberti P, Binda D, Bidoli P, Cazzaniga M, Cortinovis D, Bruna J, Velasco R, Argyriou AA, Kalofonos HP, Psimaras D, Ricard D, Pace A, Gali\u0026egrave; E, Briani C, Lucchetta M, Campagnolo M, Dalla Torre C, Merkies ISJ, Faber CG, Merkies ISJ, Vanhoutte EK, Bakkers M, Brouwer B, Lalisang RI, Boogerd W, Brandsma D, Koeppen S, Hense J, Grant R, Storey D, Kerrigan S, Schenone A, Reni L, Piras B, Fabbri S, Padua L, Granata G, Leandri M, Ghignotti I, Plasmati R, Pastorelli F, Postma TJ, Heimans JJ, Eurelings M, Meijer RJ, Grisold W, Lindeck Pozza E, Mazzeo A, Toscano A, Tomasello C, Altavilla G, Penas Prado M, Dominguez Gonzalez C, Dorsey SG, Brell JM. 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Rasch model-based testing of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire\u0026ndash;Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20) using Alliance for Clinical Trials in Oncology (Alliance) A151408 study data. Support Care Cancer 2019;27:2599\u0026ndash;2608. doi:10.1007/s00520-018-4553-y.\u003c/li\u003e\n\u003cli\u003eStansfield B, Hawkins K, Adams S, Bhatt H. A mixed linear modelling characterisation of gender and speed related changes in spatiotemporal and kinematic characteristics of gait across a wide speed range in healthy adults. Med Eng Phys 2018;60:94\u0026ndash;102. doi:10.1016/j.medengphy.2018.07.015.\u003c/li\u003e\n\u003cli\u003eTofthagen C, Overcash J, Kip K. Falls in persons with chemotherapy-induced peripheral neuropathy. Support Care Cancer 2012;20:583\u0026ndash;589. doi:10.1007/s00520-011-1127-7.\u003c/li\u003e\n\u003cli\u003eVu PD, McDonough KE, Dougherty PM, D\u0026rsquo;Souza RS, Javed S. Psychophysical and Functional Outcomes in Chemotherapy-induced Peripheral Neuropathy After Spinal Cord Stimulation: A Narrative Review and Case Series. Neuromodulation Technol Neural Interface 2024;27:1305\u0026ndash;1320. doi:10.1016/j.neurom.2024.06.006.\u003c/li\u003e\n\u003cli\u003eWang M, Molassiotis A. Mapping chemotherapy-induced peripheral neuropathy phenotype and health-related quality of life in patients with cancer through exploratory analysis of multimodal assessment data. Support Care Cancer 2022;30:4007\u0026ndash;4017. doi:10.1007/s00520-022-06821-0.\u003c/li\u003e\n\u003cli\u003eWinters-Stone KM, Horak F, Jacobs PG, Trubowitz P, Dieckmann NF, Stoyles S, Faithfull S. Falls, Functioning, and Disability Among Women With Persistent Symptoms of Chemotherapy-Induced Peripheral Neuropathy. J Clin Oncol Off J Am Soc Clin Oncol 2017;35:2604\u0026ndash;2612.\u003c/li\u003e\n\u003cli\u003eWozniak KM, Vornov JJ, Wu Y, Liu Y, Carozzi VA, Rodriguez-Menendez V, Ballarini E, Alberti P, Pozzi E, Semperboni S, Cook BM, Littlefield BA, Nomoto K, Condon K, Eckley S, DesJardins C, Wilson L, Jordan MA, Feinstein SC, Cavaletti G, Polydefkis M, Slusher BS. Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery. Cancer Res 2018;78:817\u0026ndash;829. doi:10.1158/0008-5472.CAN-17-1467.\u003c/li\u003e\n\u003cli\u003eWright MJ, Twose DM, Gorter JW. Gait characteristics of children and youth with chemotherapy induced peripheral neuropathy following treatment for acute lymphoblastic leukemia. Gait Posture 2017;58:139\u0026ndash;145. doi:10.1016/j.gaitpost.2017.05.004.\u003c/li\u003e\n\u003cli\u003eZahiri M, Chen KM, Zhou H, Nguyen H, Workeneh BT, Yellapragada SV, Sada YH, Schwenk M, Najafi B. Using wearables to screen motor performance deterioration because of cancer and chemotherapy-induced peripheral neuropathy (CIPN) in adults - Toward an early diagnosis of CIPN. J Geriatr Oncol 2019;10:960\u0026ndash;967. doi:10.1016/j.jgo.2019.01.010.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6666978/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6666978/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eChemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating side effect of neurotoxic chemotherapeutic agents. Patient-reported outcome (PRO) measures are widely utilized to assess CIPN severity; however, they are subject to bias and variability. This prospective case series investigates whether gait parameters provide an objective measure of CIPN severity. This pilot study consisted of 27 patients: 9 active CIPN, 9 CIPN resolved, and 9 healthy controls. Gait parameters including velocity, ambulation time, cadence, distance, and number of steps were assessed using GAITRite®. Treatment-Induced Neuropathy Assessment Scale (TNAS) pain and PROMIS® 29+2 Profile v2.1 (PROPr)\u003cstrong\u003e \u003c/strong\u003escores were collected and correlated with gait measures. Patients with active CIPN exhibited significant gait impairments compared to both CIPN-resolved and healthy control groups. Active CIPN patients exhibited significantly slower velocity, greater step count, shorter walking distance, and longer ambulation time as compared to both CIPN-resolved and healthy control groups. Active CIPN patients also had higher cadence than healthy controls. TNAS pain scores were significantly negatively correlated with velocity and positively correlated with ambulation time in active CIPN patients. PROPr domains (pain intensity, pain interference, and physical function) were significantly correlated with velocity and ambulation time. Our preliminary findings demonstrate the potential for gait parameters to serve as an objective and relatively quick method for assessing CIPN severity. Further studies with a larger and more diverse sample will be necessary to establish gait as a clinical tool for evaluating severity, functional decline, and recovery in CIPN patients.\u003c/p\u003e","manuscriptTitle":"Gait as a Quantitative Indicator of the Severity of Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-01 08:04:49","doi":"10.21203/rs.3.rs-6666978/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-22T16:53:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-22T00:19:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-09T22:45:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"134834382735212614281545026789999377308","date":"2025-12-08T04:32:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"242546670277404642724045489717898094920","date":"2025-11-17T03:33:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"111317415235042290392708479498816469890","date":"2025-07-05T07:46:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-25T00:24:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-25T00:21:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-23T04:17:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2025-05-14T19:32:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"92e160c5-f709-483d-aad8-0e78f02304ed","owner":[],"postedDate":"July 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:01:55+00:00","versionOfRecord":{"articleIdentity":"rs-6666978","link":"https://doi.org/10.1007/s00520-026-10507-2","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2026-03-03 15:58:34","publishedOnDateReadable":"March 3rd, 2026"},"versionCreatedAt":"2025-07-01 08:04:49","video":"","vorDoi":"10.1007/s00520-026-10507-2","vorDoiUrl":"https://doi.org/10.1007/s00520-026-10507-2","workflowStages":[]},"version":"v1","identity":"rs-6666978","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6666978","identity":"rs-6666978","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}