Chemotherapy-Induced Peripheral Neuropathy and Falls in Cancer Survivors Relate to Digital Balance and Gait Impairments.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) and falls can be persistent side effects of cancer treatment. Standing postural sway and gait tests with body-worn, inertial sensors provide objective digital balance and gait measures that represent several different domains controlling mobility. Specific domains of balance and gait that related to neuropathy and falls are unknown. The aim of this study was to determine which domains of balance and gait differed between cancer survivors who report (1) CIPN symptoms versus no symptoms, (2) a history of falls in the past 6 months versus no falls, and (3) prospective falls over 12 months versus no falls. METHODS: Postural sway during 30 seconds of quiet standing and gait characteristics from a 7-m timed up and go test were recorded with six synchronized inertial sensors (Opals by APDM Wearable Technologies, a Clario Company) in 425 older, female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used to identify independent domains of mobility from 15 balance and gait measures. RESULTS: PCA analysis revealed five independent domains (PC1 = sway amplitude, PC2 = gait pace, PC3 = sway frequency, PC4 = gait spatial-temporal, and PC5 = turning) that accounted for 81% of the variance of performance. Cancer survivors who reported CIPN symptoms had significantly higher sway frequency (PC3) than asymptomatic survivors. Past fallers had significantly larger sway area (PC1) and slower gait pace (PC2) than nonfallers. Prospective fallers showed a significantly smaller stride length (PC4) than nonfallers. CONCLUSION: Digital balance and gait measures using wearable sensors during brief standing and walking tests provide objective metrics of CIPN-related mobility impairment and fall risk that could be useful for oncology clinical trials.

Assessment of Mobility Trajectories Using Wearable Inertial Sensors During Autologous Hematopoietic Cell Transplant.

OBJECTIVE: This study aimed to characterize mobility patterns using wearable inertial sensors and serial assessment across autologous hematopoietic cell transplant (autoHCT) and investigate the relation between mobility and perceived function in patients with hematologic cancer. DESIGN: Prospective longitudinal study. SETTING: Hospital adult transplant clinic followed by discharge. PARTICIPANTS: 78 patients with hematological cancer receiving autoHCT. MAIN OUTCOME MEASURES: Mobility was measured across 3 clinical phases (pretransplant, pre-engraftment, and post-engraftment) in using inertial sensors worn during prescribed performance tests in the hospital. Perceived function was assessed using validated provider-reported (Eastern Cooperative Oncology Group [ECOG] Performance Status Scale) and patient-reported [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]) measures. Trajectories of 5 selected mobility characteristics (turn duration, gait speed, stride time variability, double support time, and heel strike angle) across the clinical phases were also evaluated using piecewise linear mixed-effects models. RESULTS: Using Principal Components Analysis, 4 mobility patterns were identified pretransplant: Gait Limitation, Sagittal Sway, Coronal Sway, and Balance Control. Gait Limitation measured pretransplant was significantly inversely associated with perceived function reported by the provider- (ß = -0.11; 95% CI: -0.19, -0.02) and patient- (ß = -4.85; 95% CI: -7.72, -1.99) post-engraftment in age-adjusted linear regression models. Mobility characteristics demonstrated immediate declines early pre-engraftment with stabilization by late pre-engraftment. CONCLUSION: Patients with hematological cancer experiencing gait limitations pretransplant are likely to have worse perceived function post-engraftment. Mobility declines in early phases post-transplant and may not fully recover, indicating an opportunity for timely rehabilitation referrals. Wearable inertial sensors can be used to identify early mobility problems and patients who may be at risk for future functional decline who may be candidates for early physical rehabilitation.

Using Wearable Inertial Sensors to Assess Mobility of Patients With Hematologic Cancer and Associations With Chemotherapy-Related Symptoms Before Autologous Hematopoietic Stem Cell Transplant: Cross-sectional Study.

BACKGROUND: Wearable sensors could be a simple way to quantify and characterize mobility in patients with hematologic cancer scheduled to receive autologous hematopoietic stem cell transplant (autoHSCT) and how they may be related to common treatment-related symptoms and side effects of induction chemotherapy. OBJECTIVE: We aimed to conduct a cross-sectional study comparing mobility in patients scheduled to receive autoHSCT with that in healthy, age-matched adult controls and determine the relationships between patient mobility and chemotherapy-related symptoms. METHODS: Patients scheduled to receive autoHSCT (78/156, 50%) and controls (78/156, 50%) completed the prescribed performance tests using wearable inertial sensors to quantify mobility including turning (turn duration and number of steps), gait (gait speed, stride time, stride time variability, double support time, coronal trunk range of motion, heel strike angle, and distance traveled), and balance (coronal sway, coronal range, coronal velocity, coronal centroidal frequency, sagittal sway, sagittal range, sagittal velocity, and sagittal centroidal frequency). Patients completed the validated patient-reported questionnaires to assess symptoms common to chemotherapy: chemotherapy-induced peripheral neuropathy (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale), nausea and pain (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire), fatigue (Patient-Reported Outcomes Measurement Information System Fatigue Short Form 8a), vertigo (Vertigo Symptom Scale-short form), and depression (Center for Epidemiological Studies-Depression). Paired, 2-sided t tests were used to compare mobility between patients and controls. Stepwise multivariable linear regression models were used to evaluate associations between patient mobility and symptoms. RESULTS: Patients aged 60.3 (SD 10.3) years had significantly worse turning (turn duration; P<.001), gait (gait speed, stride time, stride time variability, double support time, heel strike angle, stride length, and distance traveled; all P<.001), and balance (coronal sway; P<.001, range; P<.001, velocity; P=.02, and frequency; P=.02; and sagittal range; P=.008) than controls. In patients, high nausea was associated with worse stride time variability (ß=.001; P=.005) and heel strike angle (ß=-.088; P=.02). Pain was associated with worse gait speed (ß=-.003; P=.003), stride time variability (ß=.012; P=.02), stride length (ß=-.002; P=.004), and distance traveled (ß=-.786; P=.005). Nausea and pain explained 17% to 33% and 14% to 36% of gait variance measured in patients, respectively. CONCLUSIONS: Patients scheduled to receive autoHSCT demonstrated worse mobility in multiple turning, gait, and balance domains compared with controls, potentially related in part to nausea and pain. Wearable inertial sensors used in the clinic setting could provide granular information about mobility before further treatment, which may in turn benefit from rehabilitation or symptom management. Future longitudinal studies are needed to better understand temporal changes in mobility and symptoms across the treatment trajectory to optimally time, design, and implement strategies, to preserve functioning in patients with hematologic cancer in the long term.

Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention.

PURPOSE/OBJECTIVES: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention. MATERIALS AND METHODS: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50-75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments. RESULTS: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not. CONCLUSIONS: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.

Remote administration of physical performance tests among persons with and without a cancer history: Establishing reliability and agreement with in-person assessment.

OBJECTIVES: To assess the reliability of using videoconference technology to remotely administer the Short Physical Performance Battery (SPPB), including the 5-time sit-to-stand (5XSTS) and usual 4-m walk (4mWT), and the Timed Up and Go (TUG) tests and agreement with in-person administration among adults with and without cancer. METHODS: Participants from two ongoing clinical exercise trials in cancer survivors, one that included partners without cancer, comprised the available sample (n = 176; mean age 62.5 ± 11.5 years.). Remote tests were administered on two separate days by either the same or a different assessor to determine intra-rater and inter-rater reliability, respectively. We also compared tests conducted remotely and in-person using the same assessor and the same participant. Intraclass correlation coefficients (ICC) and 95% confidence intervals (95% CI) were used for all comparisons, except for the SPPB score, which used Cohen's kappa and Krippendorf's alpha for intra- and inter-rater reliability, respectively. RESULTS: Remote assessment of the TUG test had excellent intra-rater reliability (0.98, 95% CI 0.93-0.99), inter-rater reliability (ICC = 0.96, 95% CI 0.90-0.99), and good agreement with in-person tests (ICC = 0.88, 95% CI 0.74-0.94). The 5XSTS and 4mWT showed excellent (ICC = 0.92, 95% CI 0.84-0.96) and good (ICC = 0.87, 95% CI 0.71-0.94) intra-rater reliability, respectively, but somewhat lower inter-rater reliability (5XSTS: ICC = 0.65, 95% CI 0.34-0.83 and 4mWT: ICC = 0.62, 95% CI 0.30-0.81). Remote 5XSTS had moderate agreement (ICC = 0.72, 95% CI 0.62-0.80) and 4mWT had poor agreement (ICC = 0.48, 95% CI -0.07-0.76) with in-person tests. CONCLUSIONS: Remote assessment of common physical function tests in older adults, including those who have cancer, is feasible and highly reliable when using the same assessor. TUG may be the most methodologically robust measure for remote assessment because it is also highly reliable when using different assessors and correlates strongly with in-person testing. Adapting administration of objective measures of physical function for the remote environment could significantly expand the reach of research and clinical practice to assess populations at risk of functional decline.

Postural sway, falls, and self-reported neuropathy in aging female cancer survivors.

BACKGROUND: Falls are a major public health concern in older adults, and the proportion of older adults that has been diagnosed with cancer is growing. Yet, while falls, peripheral neuropathy, and postural instability are more common in aging cancer survivors, it is unclear how these factors interact. RESEARCH QUESTION: Our objective was to examine how components of sway related to self-reported neuropathy and falls. METHODS: Postural sway during static stance was recorded with an inertial sensor (APDM Opal), placed on the lumbar spine region in 434 older female cancer survivors (mean age 63) and 49 healthy older female control subjects (mean age 63). Measures of sway were resolved into principal components that were compared between women with and women without self-reported falls in the previous 6 months and between those with and without self-reported symptoms of peripheral neuropathy. RESULTS: Cancer survivors had worse sway than healthy control subjects in components related to sway magnitude and mediolateral frequency of sway, but no difference in the component related to resultant / AP sway jerk and frequency. Cancer survivors who reported neuropathy were more likely to have higher resultant / AP sway frequencies and jerk than asymptomatic survivors, while survivors who reported a fall were more likely to have lower frequencies of mediolateral sway than non-fallers. Falls were more strongly associated with mediolateral sway in survivors with more severe neuropathy; whereas falls were more strongly associated with resultant / AP sway frequency in survivors with less severe neuropathy SIGNIFICANCE: Postural stability, falls, and neuropathy have complex interactions that can vary across components of postural sway. While the frequency of mediolateral sway was associated with falls across our entire cohort, neuropathy influenced the associations between specific characteristics of sway and falls, which may have implications for fall prevention interventions.

Design and evaluation of a portable smart-phone based peripheral neuropathy test platform.

In this paper, we describe a novel portable test platform that can be used to test peripheral neuropathy either within a clinic or at home. The system, called the PeriVib, is comprised of (1) a small, custom vibration motor designed to apply a vibration stimulus to the toe with constant pressure to test sensation threshold, and (2) a custom smart-phone app that enables a patient to run a series of functional gait and balance tests. Vibration is applied by PeriVib in two separate modes. The first mode, ramp-up, starts at zero amplitude and increases to a maximum level while the patient indicates when they start feeling the pressure by lifting their finger off the touch-screen on the phone. The second mode, ramp-down, starts at a maximal intensity and decreases in intensity; the patient indicates when they stop feeling the vibration. The smart-phone app determines the patient's threshold by recording the vibration amplitude when they indicate the onset or loss of vibratory sensation, depending on the mode. In both modes, the measurement is repeated five times. In addition to controlling the vibration motor during the vibration test, the smart phone app also enables collection of gait and sway metrics through the use of the accelerometer and gyroscope sensors on the smartphone. The entire set of tests requires approximately 5 minutes to complete and can be done by a patient with minimal instructions from a clinician. In a cohort of 28 subjects with a history of chemotherapy-induced peripheral neuropathy, we compared the PeriVib performance with two established threshold sensing systems: (1) a Biothesiometer device and (2) a tuning fork. We found that the sensation threshold estimated by PeriVib correlated well with the Biothesiometer ($\mathrm{R}^{2}$ of 0.68) but less well with the tuning fork ($\mathrm{R}^{2}$ of 0.15). Functional gait and balance metrics did not correlate with peripheral neuropathy severity.