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Cancer-related fatigue is a prevalent, debilitating condition, and preliminary evidence suggests a relationship between higher diet quality and lower fatigue. Serum-based carotenoids, Vitamin A, and Vitamin E are biomarkers of fruit and vegetable intake and therefore diet quality. To further elucidate the link between diet quality and cancer-related fatigue, associations were assessed between these serum-based nutrients and fatigue among American adults with special attention to cancer history. Data were analyzed from the United States 2005–2006 National Health and Nutrition Examination Survey dataset. Ten carotenoids, vitamin A, vitamin E, and γ-tocopherol were measured from fasting blood samples and fatigue was patient-reported. Associations between carotenoid concentration and fatigue were estimated using ordinal logistic regression models. Adjusted models included a diagnosis of cancer (with the exception on nonmelanoma skin cancer, yes/no), age, body mass index, race/ethnicity, education, and exercise habits as covariates, and additional models included a cancer × nutrient interaction. Of 4,091 participants, 272 (8.0%) reported a history of cancer. Greater fatigue was associated with lower serum trans-lycopene, retinyl palmitate, and retinyl stearate (all P < 0.05) in separate models adjusting for potential confounders. For these nutrients, a one-SD increase in nutrient was associated with a 6.8%–9.9% lower risk of greater fatigue. Among cancer survivors only (n = 272), statistically significant associations were not observed between any of the nutrients and fatigue. In conclusion, greater serum concentrations of carotenoid biomarkers were associated with less fatigue. These results support further exploration into relationships between carotenoid intake, diet quality, and persistent fatigue.Significance:Cancer-related fatigue often persists for years into survivorship, reduces quality of life, and prevents people from returning to their lives before cancer. Interventions to address cancer-related fatigue are much needed. Herein, serum carotenoids were associated with lower fatigue, thereby supporting further development of nutritional interventions to address fatigue in survivorship.

Suppl. Table 1. Results of crude and adjusted models describing the association between carotenoid concentrations and fatigue: all model output. For body mass index, estimates are compared to normal weight (18.5-Suppl. Table 2. Results of adjusted model with the nutrient×cancer interaction term to explore the associations between carotenoids and cancer-related fatigue: all model output.Suppl. Table 3. Adjusted odds ratios and 95% confidence intervals for the effects of the nutrient×cancer interaction on fatigue. Models are adjusted for age, body mass index, race/ethnicity, education, physical activity, history of a cancer diagnosis, and nutrient concentration.Suppl. Table 4. Results of adjusted models (no interaction term) describing the association between carotenoid concentrations and fatigue only among cancer survivors: all model output; estimates for race/ethnicity are compared to non-Hispanic Whites, 1=Mexican American, 2=Other Hispanic, 4=non-Hispanic Black American, 5=Other non-Hispanic race, including multi-racial; estimates for body mass index are compared to those of normal weight; and estimates for education are compared to those with at least a college education. Exercise is estimated from metabolic equivalents (MET hours) per week as a continuous variable. Age, Years since Diagnosis, and carotenoid concentration are treated as continuous variables. (n=272)

Cancer-related fatigue is a prevalent, debilitating condition, and preliminary evidence suggests a relationship between higher diet quality and lower fatigue. Serum-based carotenoids, Vitamin A, and Vitamin E are biomarkers of fruit and vegetable intake and therefore diet quality. To further elucidate the link between diet quality and cancer-related fatigue, associations were assessed between these serum-based nutrients and fatigue among American adults with special attention to cancer history. Data were analyzed from the United States 2005–2006 National Health and Nutrition Examination Survey dataset. Ten carotenoids, vitamin A, vitamin E, and γ-tocopherol were measured from fasting blood samples and fatigue was patient-reported. Associations between carotenoid concentration and fatigue were estimated using ordinal logistic regression models. Adjusted models included a diagnosis of cancer (with the exception on nonmelanoma skin cancer, yes/no), age, body mass index, race/ethnicity, education, and exercise habits as covariates, and additional models included a cancer × nutrient interaction. Of 4,091 participants, 272 (8.0%) reported a history of cancer. Greater fatigue was associated with lower serum trans-lycopene, retinyl palmitate, and retinyl stearate (all P < 0.05) in separate models adjusting for potential confounders. For these nutrients, a one-SD increase in nutrient was associated with a 6.8%–9.9% lower risk of greater fatigue. Among cancer survivors only (n = 272), statistically significant associations were not observed between any of the nutrients and fatigue. In conclusion, greater serum concentrations of carotenoid biomarkers were associated with less fatigue. These results support further exploration into relationships between carotenoid intake, diet quality, and persistent fatigue. Significance: Cancer-related fatigue often persists for years into survivorship, reduces quality of life, and prevents people from returning to their lives before cancer. Interventions to address cancer-related fatigue are much needed. Herein, serum carotenoids were associated with lower fatigue, thereby supporting further development of nutritional interventions to address fatigue in survivorship.

INTRODUCTION: Chemotherapy-induced peripheral neurotoxicity (CIPN) remains a significant toxicity in cancer survivors without preventative strategies or rehabilitation. Exercise and physical activity-based interventions have demonstrated promise in reducing existing CIPN symptoms and potentially preventing toxicity, however there is a significant gap in evidence due to the lack of quality clinical trials and appropriate outcome measures. AREAS COVERED: The authors systematically reviewed outcome measures in CIPN exercise and physical rehabilitation studies with expert panel consensus via the Peripheral Nerve Society Toxic Neuropathy Consortium to provide recommendations for future trials. Across 26 studies, 75 outcome measures were identified and grouped into 16 domains within three core areas - measures of manifestations of CIPN (e.g. symptoms/signs), measures of the impact of CIPN and other outcome measures. EXPERT OPINION: This article provides a conceptual framework for CIPN outcome measures and highlights the need for definition of a core outcome measures set. The authors provide recommendations for CIPN exercise and physical rehabilitation trial design and outcome measure selection. The development of a core outcome measure set will be critical in the search for neuroprotective and treatment approaches to support cancer survivors and to address the significant gap in the identification of effective rehabilitation and treatment options for CIPN.

Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a highly prevalent, dose-limiting, costly, and tough-to-treat adverse effect of several chemotherapy agents, presenting as sensory and motor dysfunction in the distal extremities. Due to limited effective treatments, CIPN can permanently reduce patient function, independence, and quality of life. One of the most promising interventions for CIPN is physical therapy which includes exercise, stretching, balance, and manual therapy interventions. Currently, there are no physical therapy guidelines for CIPN, thus limiting its uptake and potential effectiveness. Methods: Utilizing the authors’ collective expertise spanning physical therapy, symptom management research, oncology, neurology, and treating patients with CIPN, we propose a comprehensive clinical workflow for physical therapists to assess and treat CIPN. This workflow is based on (1) physical therapy guidelines for treating neurologic symptoms like those of CIPN, (2) results of clinical research on physical therapy and exercise, and (3) physical therapy clinical judgement. Results: We present detailed tables of pertinent physical therapy assessment and treatment methods that can be used in clinical settings. CIPN assessment should include detailed sensory assessment, objective strength assessments of involved extremities, and validated physical performance measures incorporating static and dynamic balance, gait, and functional mobility components. CIPN treatment should involve sensorimotor, strength, balance, and endurance-focused interventions, alongside a home-based exercise prescription that includes aerobic training. We conclude with action items for oncology teams, physical therapists, patients, and researchers to best apply this framework to address CIPN. Conclusions: Physical therapists are in a unique position to help assess, prevent, and treat CIPN given their training and prevalence, yet there are no physical therapy clinical practice guidelines for CIPN. Our preliminary suggestions for CIPN assessments and treatments can catalyze the development of guidelines to assess and treat CIPN. We urge oncology teams, physical therapists, patients, and researchers to develop, adapt, and disseminate this framework to help alleviate the burden of chemotherapy on patients with cancer.

Cancer-related fatigue is a common, burdensome symptom of cancer and a side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I–III cancer and at least six weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence (score 0–14), dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and four weeks. Participants (n = 33) were 51.0 ± 14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at four and eight weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8 (ES = 0.31, 0.25, respectively). For those with a baseline MedDiet score

Purpose. Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of taxane and platinum chemotherapy for breast cancer. Clinicians cannot accurately predict CIPN severity partly because its pathophysiology is poorly understood. Although inflammation may play a role in CIPN, there are limited human studies. Here, we identified the strongest predictors of CIPN using variables measured before taxane- or platinum-based chemotherapy, including serum inflammatory markers.Methods. 116 sedentary women with breast cancer (mean age 55 years) rated (1) numbness and tingling and (2) hot/coldness in hands/feet on 0-10 scales before and after six weeks of taxane- or platinum-based chemotherapy. A sub-study was added to collect cytokine data in the final 55 patients. We examined all linear models to predict CIPN severity at 6 weeks using pre-chemotherapy assessments of inflammatory, behavioral, clinical, and psychosocial factors. The final model was selected via goodness of fit.Results. The strongest pre-chemotherapy predictors of numbness and tingling were worse fatigue/anxiety/depression (explaining 27% of variance), older age (9%), and baseline neuropathy (5%). The strongest predictors of hot/coldness in hands/feet were worse baseline neuropathy (11%) and fatigue/anxiety/depression (6%). Inflammation was a risk for CIPN, per more pro-inflammatory IL-1β (6%) predicting numbness/tingling and less anti-inflammatory IL-10 predicting numbness and tingling (6%) and hot/coldness in hands/feet (9%).Conclusions. The strongest pre-chemotherapy predictors of CIPN included worse fatigue/anxiety/depression and baseline neuropathy. A pro-inflammatory state also predicted CIPN. Because this is an exploratory study, these results suggest specific outcomes (e.g., IL-1β) and effect size estimates for designing replication and extension studies.Trial Registration. NCT00924651

Purpose Cancer-related fatigue is a prevalent, debilitating condition that can persist for months or years after treatment. In a single-arm clinical trial, the feasibility and safety of a time-restricted eating (TRE) intervention were evaluated among cancer survivors, and initial estimates of within-person change in cancer-related fatigue were obtained. Methods Participants were 4–60 months post-cancer treatment, were experiencing fatigue (≥ 3 on a scale 0–10), and were not following TRE. TRE entailed limiting all food and beverages to a self-selected 10-h window for 14 days. Participants reported their eating window in a daily diary and completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Brief Fatigue Inventory (BFI), and symptom inventory pre- and post-intervention. Results Participants (n = 39) were 61.5 ± 12.4 years old and 1.8 ± 1.3 years post-treatment; 89.7% had had breast cancer. The intervention was feasible in that 36/39 (92.3%) of participants completed all questionnaires and daily diaries. It was also safe with no severe adverse events or rapid weight loss (average loss of 1.1 ± 2.3 pounds, p = 0.008). Most adhered to TRE; 86.1% ate within a 10-h window at least 80% of the days, and the average eating window was 9.33 ± 1.05 h. Fatigue scores improved 5.3 ± 8.1 points on the FACIT-F fatigue subscale (p p p

Is there a universal mapping of physiology to emotion, or do these mappings vary substantially by person or situation? Psychologists, philosophers, and neuroscientists have debated this question for decades. Most previous studies have focused on differentiating emotions on the basis of accompanying autonomic responses using analytical approaches that often assume within-category homogeneity. In the present study, we took an alternative approach to this question. We determined the extent to which the relationship between subjective experience and autonomic reactivity generalizes across or depends upon the individual and situation for instances of a single emotion category, specifically, fear. Electrodermal activity and cardiac activity - two autonomic measures that are often assumed to show robust relationships with instances of fear - were recorded while participants reported fear experience in response to dozens of fear-evoking videos related to three distinct situations: spiders, heights, and social encounters. We formally translated assumptions from diverse theoretical models into a common framework for model comparison analyses. Results exceedingly favored a model that assumed situation-dependency in the relationship between fear experience and autonomic reactivity, with subject variance also significant, but constrained by situation. Models that assumed generalization only across situations or individuals performed much worse by comparison. These results call into question the assumption of generalizability of autonomic-subjective mappings across instances of fear, such as in translational research from non-human animals to humans, and suggest the benefits of adopting a situated approach to understanding the autonomic correlates of fear experience.

Background Inflammation may contribute to cognitive difficulties in patients with breast cancer. We tested 2 hypotheses: inflammation is elevated in patients with breast cancer vs noncancer control participants and inflammation in patients is associated with worse attention and processing speed over the course of chemotherapy. Methods Serum cytokines (interleukin [IL]–4, 6, 8, 10; tumor necrosis factor [TNF]–α) and soluble receptors [sTNFRI, II]) were measured in 519 females with breast cancer before and after chemotherapy and 338 females without cancer serving as control participants. Attention and processing speed were measured by Rapid Visual Processing (RVP), Backward Counting (BCT), and Trail Making-A (TMT-A) tests. Linear regression models examined patient vs control cytokines and receptor levels, adjusting for covariates. Linear regression models also examined relationships between patient cytokines and receptor levels and test performance, adjusting for age, body mass index, anxiety, depression, cognitive reserve, and chemotherapy duration. Statistical tests were 2-sided (α = .05). Results sTNFRI and sTNFRII increased over time in patients relative to controls, whereas IL-4, IL-6, and IL-10 decreased. Prechemotherapy, higher IL-8 associated with worse BCT (β = 0.610, SE = 0.241, P = .01); higher IL-4 (β = −1.098, SE = 0.516, P = .03) and IL-10 (β = −0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (β = 0.841, SE = 0.260, P = .001), sTNFRI (β = 6.638, SE = 2.208, P = .003), and sTNFRII (β = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (β = −1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (β = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (β = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (β = −0.564, SE = 0.253, P = .03). Conclusions Generally, worse attention and processing speed were associated with higher inflammatory cytokines and receptors and lower anti-inflammatory cytokines in patients; future confirmatory studies are needed.

Pharmacological strategies for chemotherapy-induced peripheral neurotoxicity (CIPN) are very limited. We systematically reviewed data on rehabilitation, exercise, physical therapy, and other physical non-pharmacological interventions and offered evidence-based recommendations for the prevention and treatment of CIPN. A literature search using PubMed, Web of Science and CINAHL was conducted from database inception until May 31st, 2021. 2791 records were title-abstract screened, 71 papers were full-text screened, 41 studies were included, 21 on prevention and 20 on treatment of CIPN. Treatment type, cancer type, chemotherapy compounds were heterogeneous, sample size was small (median: N = 34) and intention-to-treat analysis was lacking in 26/41 reports. Because of the methodological issues of included studies, the reviewed evidence should be considered as preliminary. Exercise, endurance, strength, balance, and sensorimotor training have been studied in low-to-moderate quality studies, while the evidence for other treatments is preliminary/inconclusive. We offer recommendation for the design of future trials on CIPN.

Cancer-related fatigue is a prevalent and debilitating condition that persists for years into survivorship. Studies evaluating both fish oil supplementation on fatigue and associations between fish oil consumption and fatigue have shown mixed effects; it is unknown what factors contribute to these differential effects. Herein, we investigate whether the nutritional status of cancer survivors was associated with serum omega-3 concentration or change in serum omega-3s throughout a fish oil supplementation study, and then if any of these factors were associated with fatigue. Breast cancer survivors 4–36 months post-treatment with moderate-severe fatigue were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g of each daily for 6 weeks. Baseline nutritional status was calculated using the Controlling Nutritional Status tool (serum albumin, lymphocytes, cholesterol). At baseline and post-intervention, serum fatty acids were quantified and fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Participants (n = 85) were 61.2 ± 9.7 years old with a body mass index of 31.9 ± 6.7 kg/m2; 69% had a good nutritional score and 31% had light-moderate malnutrition. Those with good nutritional status had greater total serum omega-3s at baseline (p = 0.013) and a greater increase in serum omega-3s with supplementation (p = 0.003). Among those who were supplemented with fish oil, greater increases in serum omega-3s were associated with greater improvements in fatigue. In conclusion, good nutritional status may increase uptake of fatty acid supplements, increasing their ability to improve fatigue.

Purpose To quantify the impact of diabetes on the trajectory of cancer-related fatigue (CRF) from pre-chemotherapy to 6 months post-chemotherapy for patients with breast cancer compared to non-cancer controls.Methods This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and age-matched women without cancer (controls). CRF was measured using the Multidimensional Fatigue Symptom Inventory (MFSI) pre-, post-, and 6-months post-chemotherapy in patients; controls were assessed at equivalent time points. Diabetes status was obtained at baseline. Repeated measures mixed models estimated the association between CRF and diabetes controlling for cancer (y/n), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education.Results A total of 439 patients and 235 controls (age: 52.8±10.5 years) had available data on diabetes status. Diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). Patients had worse fatigue than controls throughout treatment (p Diabetes was associated with worse CRF with a clinically meaningful difference of 4.7±1.7 points on the fatigue measure in all participants (p=0.009) and patients alone (p=0.030). For MFSI subdomains, diabetes was associated with worse general (p=0.002), physical (p=0.005), and mental fatigue (p=0.025) but not worse emotional fatigue or vigor (p>0.14) among patients. Conclusions Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe CRF in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address CRF during chemotherapy treatment

Psychophysiologists often record electrodermal activity (EDA) exosomatically to derive measures of slow, tonic activity—skin conductance level (SCL)—and faster, more punctate changes—skin conductance responses (SCRs). An SCR is considered relevant when its amplitude exceeds a researcher-determined threshold (e.g., 0.05 μS), typically fixed across study participants and conditions. However, fixed SCR thresholds may detect more SCRs in samples with higher SCL because the number and amplitude of SCRs correlate positively with SCL. To address this issue, we developed a novel fixed plus adaptive (FA) thresholding method that adjusts SCR detection as a function of the prevailing SCL. We hypothesized greater statistical power to detect a difference in the rate of SCRs across high vs. low arousal stimuli using FA thresholding compared to fixed thresholding. Study 1 consisted of 254 young adults measured in a laboratory using wired EDA sensors during exposure to evocative images and sounds. Study 1 constituted our exploratory dataset, wherein we found an optimal FA threshold of 1.9% that maximized the ability to detect a difference in SCR rate between high vs. low arousal stimuli. Study 2 involved 20 children with autism repeatedly measured in a clinic using wireless EDA sensors during several behavioral tasks. Study 2 constituted our validation dataset, wherein FA thresholding at 1.9% increased statistical power to detect a difference in SCR rate between high vs. low arousal tasks, compared to fixed thresholding at 0.05 μS. Future research should test for reproducibility and generalizability of our results in other tasks, samples, and contexts.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. METHODS: The sample included over 53,000,000 patients from two regional and one national insurer in the U.S. (>400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (Definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (Definition 2). RESULTS: CIPN incidence as measured by Definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR): 2.93 (95% CI: 2.87-2.98)). For Definition 2, these incidences were 3.6% and 0.1% (RR: 25.2 (95% CI: 22.8-27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by Definitions 1 and 2 was low compared to that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared to those who received non-neurotoxic chemotherapies was high using Definition 2. CONCLUSIONS: These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

PURPOSE: To assess the impact of obesity on cancer-related fatigue (CRF) in patients with breast cancer, through a secondary analysis of a large, longitudinal, nationwide study of breast cancer patients beginning chemotherapy. METHODS: All patients (N = 565; aged 53 ± 10.6) with breast cancer completed the multidimensional fatigue symptom inventory and the symptom inventory to measure CRF symptoms at baseline, post-chemotherapy, and 6 months post-chemotherapy. Height and weight at baseline were used to categorize subjects based on body mass index (BMI): obese (≥ 30.0 kg/m(2); n = 294), overweight (25.0–29.9 kg/m(2); n = 146), and normal weight (18.5–24.9 kg/m(2); n = 125). Multivariate regression models evaluated the relationship of obesity level to CRF over time, controlling for age, menopausal status, race, Karnofsky Performance Status, cancer stage, radiation, and exercise status. RESULTS: At baseline, the obese had significantly higher CRF symptoms than the normal weight subjects for both the Multidimensional fatigue symptom inventory (MFSI) total (obese = 11.2 vs normal weight = 6.3; p = 0.03) and Symptom Inventory (SI) (obese = 3.5 vs normal weight = 2.9; p = 0.03). Significantly higher SI fatigue scores persisted at post-chemotherapy for the obese (obese = 5.0 vs normal weight = 4.4; p = 0.02). At 6 months post-chemotherapy, the obese patients still had significantly higher SI fatigue scores (obese = 3.5 vs normal weight = 3.0; p = 0.05). CONCLUSION: Obese patients suffered greater CRF from pre-chemotherapy through 6 months post-chemotherapy. Recommendations for weight loss or weight maintenance may impact CRF levels in obese breast cancer patients before and after chemotherapy.

Introduction Black cancer survivors remain at a higher risk for secondary cancers, cancer recurrence, and comorbid conditions than non-Hispanic White survivors. Physical activity may help improve health outcomes and overall quality of life. We assessed cancer survivors’ physical activity by race/ethnicity and the effect of social determinants of health (SDH) constructs (i.e., economic stability, education, and access to health care) on physical activity. Methods This was a cross-sectional analysis of data from the 2016 Behavioral Risk Factor Surveillance System. The outcome variable was physical activity after cancer diagnosis and the predictor variables were SDH and race. Multivariable logistic regressions were used to examine associations between race and physical activity and the effect of SDH on physical activity. Results Among 3,787 cancer survivors, 91.6% self-identified as White and 8.4% as Black. Blacks were more likely than Whites to report low economic stability, low access to health care, and low health literacy (all ps Conclusions The findings suggest that though Black cancer survivors are less than White to engage in physical activity, and SDH partially explained the racial difference in physical activity behaviors. These findings highlight the need to address barriers to health-care access, economic stability, and educational attainment.

BACKGROUND/OBJECTIVE Exercise interventions improve anxiety and mood disturbances in patients with cancer. However, studies are limited in older adults with cancer. We assessed the effects of exercise on anxiety, mood, and social and emotional well-being in older patients with cancer during their first 6 weeks of chemotherapy. DESIGN Exploratory secondary analysis of a randomized controlled trial (RCT). SETTING Community oncology practices. PARTICIPANTS Older patients (aged 60 years or older) undergoing chemotherapy (N = 252). INTERVENTION Patients were randomized to Exercise for Cancer Patients (EXCAP) or usual care (control) for the first 6 weeks of chemotherapy. EXCAP is a home-based, low- to moderate-intensity progressive walking and resistance training program. MEASUREMENTS Analysis of covariance, with study arm as the factor, baseline value as the covariate, and study arm × baseline interaction, was used to evaluate arm effects on postintervention anxiety (State Trait Anxiety Inventory [STAI]), mood (Profile of Mood States [POMS]), and social and emotional well-being (Functional Assessment of Cancer Therapy-General subscales) after 6 weeks. RESULTS Median age was 67 years; 77% had breast cancer. Statistically significant group differences were observed in the STAI score (P = .001), POMS score (P = .022), social well-being (P = .002), and emotional well-being (P = .048). For each outcome, EXCAP patients with worse baseline scores had larger improvements at 6 weeks; these improvements were clinically significant for STAI score and social well-being. CONCLUSIONS Among older cancer patients receiving chemotherapy, a 6-week structured exercise program improved anxiety and mood, especially among those participants with worse baseline symptoms. Additional RCTs are needed to confirm these findings and evaluate the appropriate exercise prescription for managing anxiety, mood, and well-being in this patient population. J Am Geriatr Soc 67:1005-1011, 2019.

A growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines. This is a secondary analysis of a randomized trial studying 6 weeks of moderate-intensity walking and resistance exercise during chemotherapy compared with chemotherapy alone. At pre- and post-intervention, patients provided blood to assess serum concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, and IFN-γ, and receptor sTNFR1. We investigated relationships between cytokines using the correlations between changes in cytokine concentrations from pre- to post-intervention. We obtained complete data from 293 patients (149 randomized to exercise). Exercise strengthened the correlation between concentration changes of IL-10 and IL-6 (r = 0.44 in exercisers vs. 0.11 in controls; p = 0.001). We observed the same pattern for IL-10:IL-1β and IL-10:sTNFR1. Exercise also induced an anti-inflammatory cytokine profile, per reductions in pro-inflammatory IFN-γ (p = 0.044) and perhaps IL-1β (p = 0.099, trend-level significance). Our hypothesis-generating work suggests that regular exercise during 6 weeks of chemotherapy may cause certain cytokine concentrations to change collectively (not independently). This work enhances our understanding of relationships between cytokines and complements traditional analyses of cytokines in isolation. Future work should test for replication and relationships to patient outcomes. Clinical Trials.gov, # NCT00924651, http://www.clinicaltrials.gov .

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating, and dose-limiting side effect of many chemotherapy regimens yet has limited treatments due to incomplete knowledge of its pathophysiology. Research on the pathophysiology of CIPN has focused on peripheral nerves because CIPN symptoms are felt in the hands and feet. However, better understanding the role of the brain in CIPN may accelerate understanding, diagnosing, and treating CIPN. The goals of this review are to (1) investigate the role of the brain in CIPN, and (2) use this knowledge to inform future research and treatment of CIPN. We identified 16 papers using brain interventions in animal models of CIPN and five papers using brain imaging in humans or monkeys with CIPN. These studies suggest that CIPN is partly caused by (1) brain hyperactivity, (2) reduced GABAergic inhibition, (3) neuroinflammation, and (4) overactivation of GPCR/MAPK pathways. These four features were observed in several brain regions including the thalamus, periaqueductal gray, anterior cingulate cortex, somatosensory cortex, and insula. We discuss how to leverage this knowledge for future preclinical research, clinical research, and brain-based treatments for CIPN.

Commercially available consumer electronics in (smartwatches and wearable biosensors) are increasingly enabling acquisition of peripheral physiological and physical activity data inside and outside of laboratory settings. However, there is scant literature available for selecting and assessing the suitability of these novel devices for scientific use. To overcome this limitation, the current paper offers a framework to aid researchers in choosing and evaluating wearable technologies for use in empirical research. Our seven-step framework includes: (1) identifying signals of interest; (2) characterizing intended use cases; (3) identifying study-specific pragmatic needs; (4) selecting devices for evaluation; (5) establishing an assessment procedure; (6) performing qualitative and quantitative analyses on resulting data; and, if desired, (7) conducting power analyses to determine sample size needed to more rigorously compare performance across devices. We illustrate the application of the framework by comparing electrodermal, cardiovascular, and accelerometry data from a variety of commercial wireless sensors (Affectiva Q, Empatica E3, Empatica E4, Actiwave Cardio, Shimmer) relative to a well-validated, wired MindWare laboratory system. Our evaluations are performed in two studies (N = 10, N = 11) involving psychometrically sound, standardized tasks that include physical activity and affect induction. After applying our framework to this data, we conclude that only some commercially available consumer devices for physiological measurement are capable of wirelessly measuring peripheral physiological and physical activity data of sufficient quality for scientific use cases. Thus, the framework appears to be beneficial at suggesting steps for conducting more systematic, transparent, and rigorous evaluations of mobile physiological devices prior to deployment in studies.

Introduction Older patients with myeloid neoplasms (MN) receiving outpatient chemotherapy are at risk of experiencing treatment-related toxicities such as functional decline. A mobile health (mHealth) exercise intervention may ameliorate these toxicities. This qualitative study aimed to inform the design of a mHealth exercise intervention for this population. Methods This was a qualitative study of thirteen patients aged ≥60 years receiving hypomethylating agents for MN. EXCAP©® is a home-based walking and progressive resistance exercise program. We combined EXCAP©® with a mobile app; the combination (GO-EXCAP Mobile App) has not been previously tested. A brief verbal description about the intervention was provided to the participants but they did not perform it. Participants were interviewed and inductive thematic analysis was used to analyze the data. Results Mean age was 71.6 (SD 8.5). Three themes were identified: 1) Perceptions of the intervention feasibility, 2) Ways to leverage the app to deliver the exercise intervention, and 3) Personalized exercise goals. Walking and resistance exercises were perceived to be feasible. Patients were comfortable initiating the intervention in cycle 2 of chemotherapy, with exercise increments occurring from week 2–4 of the cycle. Ways to leverage the app to deliver EXCAP©® include 1) Video feature for exercise demonstration and interactions, and 2) Exercise data and symptom surveys to be communicated to the exercise physiologist and primary oncology team. Preservation of existing function and activity was an important goal to participants. Conclusions Our findings provide insights about the preferences of older adults with MN for a mHealth exercise intervention.

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and dose-limiting toxicity of many widely used chemotherapy regimens for the treatment of common cancers including lung, breast, prostate, gastrointestinal, and blood cancers. Symptoms include numbness, tingling, pain, and cramping in the hands and feet, as well as impaired balance and gait that collectively increase the risk of falls and compromise activities of daily living. Among the extremely limited treatment options for CIPN, exercise has emerged as a promising intervention based on a growing body of studies. Here, we review preclinical and clinical evidence on the use of exercise and related modalities for the prevention, treatment, and management of CIPN. We identified 2 studies in rodents plus 23 studies in humans, including 15 randomized studies (10 comparing exercise vs. non-exercise control), plus 19 pre-registered studies. The 10 randomized studies collectively suggest that exercise is beneficial for the treatment and prevention of CIPN with little to no side effects. However, these studies tend to be either rigorous yet small or large yet simple and exploratory, with no Phase III randomized studies published or pre-registered. Next, we discuss biological and psychosocial mechanisms by which exercise might exert its effects. We are optimistic for the trajectory of this work including seeking definitive answers to whether exercise is beneficial, what dose of exercise is needed, how it exerts its effects mechanistically, and how to best disseminate exercise to patients in the real world.

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent, severe, and dose-limiting toxicity of several chemotherapy regimens for the treatment of multiple cancers including lung, breast, prostate, gastrointestinal, blood, and others. Patients with CIPN may experience numbness, tingling, pain, and cramping in the hands and feet, as well as problems with balance and gait that increase the risk of falls, reduce physical function, and hinder activities of daily living. At this point there are extremely limited treatment options for CIPN. Fortunately, a growing body of preliminary evidence suggests that exercise, physical therapy, and occupational therapy may help prevent, treat, and manage CIPN. Although there is not definitive evidence for the benefits of exercise on CIPN due to lack of Phase III randomized controlled trials, exercise is generally helpful in the cancer treatment continuum and poses low risk for patients with the help of a qualified professional. Therefore, we present clinical suggestions in the use of exercise for CIPN, including assessments of patient risk factors and other considerations. We conclude with an example exercise prescription that a qualified exercise professional can adapt for the specific needs, risks, and abilities of each individual patient.

Introduction: Insomnia is a significant co-morbidity for cancer survivors, and can independently reduce lifespan, but there is currently no objective biochemical measure of insomnia. Circadian rhythms are 24 hour cycles that control physiologic processes including sleep. Disrupted circadian rhythms have been proposed as a cause of insomnia. Here, we describe the use of a novel biomarker, BloodCCD, to assess circadian rhythms from RNA-sequencing of blood samples from two independent clinical trials and one observational study. BloodCCD was adapted from Clock Correlation Distance (CCD), which assesses normal progression of the molecular circadian clock from gene expression in tissue samples. We used BloodCCD to interrogate whether 1) cancer patients and survivors with insomnia have disrupted circadian rhythms compared to healthy good sleepers, and 2) whether the degree of circadian disruption correlates with severity of insomnia in survivors. Methods: For BloodCCD analysis, time-series RNA-sequencing of human blood from healthy subjects were used to construct a reference correlation matrix of 42 genes which oscillate with 24-hour rhythms. To assess the Aims, RNA-sequencing from patient and survivor blood samples were compared to this reference correlation matrix to generate a BloodCCD score. A higher score indicates a further distance from a healthy clock, and thus clock disruption. For the first Aim, blood RNA-sequencing from cancer patients undergoing active treatment and survivors at least 2-months post-treatment and with insomnia were compared to healthy good sleepers. For the second Aim, blood RNA-sequencing from cancer survivors with insomnia were assessed, stratified by Insomnia Severity Index (ISI) Score into mild (ISI 10-14), moderate (ISI 15-21), and severe (ISI 22-28) insomnia. Results: Patients (n=28, 100% prostate cancer) and cancer survivors (n=497, ~72% breast cancer) had higher BloodCCD scores, indicating disrupted circadian clock, compared to healthy good sleepers (n=14), with scores of 9.98, 7.99, and 4.13, respectively. When cancer survivors were stratified by insomnia severity, those with severe insomnia (ISI 22-28) had the highest BloodCCD, 9.00, while those with moderate insomnia (ISI 15-21) had a score of 8.24 and those with mild insomnia (ISI 10-14) had the lowest score of 7.93, indicating that survivors with severe insomnia had a more disrupted circadian clock. All BloodCCD values were p < 0.001 for each value compared to reference correlation. Conclusions: BloodCCD shows promise as a biomarker to biochemically detect disrupted circadian rhythms in cancer patients and survivors, and as a readout for insomnia severity. Future studies should investigate whether BloodCCD improves in cancer survivors receiving interventions for insomnia. Funding: UG1CA189961-07S1 (NCI BIQSFP Program), UG1CA189961 (URCC NCORP), T32CA102618 (URCC T32 program), K07CA221931 Citation Format: Brian J. Altman, Javier Bautista, Eva Culakova, Kristina M. Morris, Rachel E. DeRollo, Elliot Outland, Amber Kleckner, Ian R. Kleckner, Nikesha J. Gilmore, Benjamin T. Esparaz, Charles S. Kuzma, Amy C. Vander Woude, Po-Ju Lin, Jacob J. Hughey, Karen M. Mustian. BloodCCD is a novel biomarker to detect circadian rhythm disruption in cancer survivors with insomnia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3215.

Progressive skeletal muscle wasting in cancer cachexia involves a process of dysregulated protein synthesis and breakdown. This catabolism may be the result of mal-nutrition, and an upregulation of both pro-inflammatory cytokines and the ubiquitin proteasome pathway (UPP), which can subsequently increase myostatin and activin A release. The skeletal muscle wasting associated with cancer cachexia is clinically significant, it can contribute to treatment toxicity or the premature discontinuation of treatments resulting in increases in morbidity and mortality. Thus, there is a need for further investigation into the pathophysiology of muscle wasting in cancer cachexia to develop effective prophylactic and therapeutic interventions. Several studies have identified a central role for chronic-systemic inflammation in initiating and perpetuating muscle wasting in patients with cancer. Interestingly, while exercise has shown efficacy in improving muscle quality, only recently have investigators begun to assess the impact that exercise has on chronic-systemic inflammation. To put this new information into context with established paradigms, here we review several biological pathways (e.g. dysfunctional inflammatory response, hypothalamus pituitary adrenal axis, and increased myostatin/activin A activity) that may be responsible for the muscle wasting in patients with cancer. Additionally, we discuss the potential impact that exercise has on these pathways in the treatment of cancer-related muscle wasting. Exercise is an attractive intervention for muscle wasting in this population, partially because it disrupts chronic-systemic inflammation mediated catabolism. Most importantly, exercise is a potent stimulator of muscle synthesis, and therefore this therapy may reverse muscle damage caused by cancer cachexia.

Electrodermal Activity (EDA) − an index of sympathetic nervous system arousal − is one of the primary methods used in psychophysiology to assess the autonomic nervous system [1]. While many studies collect EDA data in short, laboratory-based experiments, recent developments in wireless biosensing have enabled longer, ‘out-of-lab’ ambulatory studies to become more common [2] . Such ambulatory methods are beneficial in that they facilitate more longitudinal and environmentally diverse EDA data collection. However, they also introduce challenges for efficiently and accurately identifying discrete skin conductance responses (SCRs) and measurement artifacts, which complicate analyses of ambulatory EDA data. Therefore, interest in developing automated systems that facilitate analysis of EDA signals has increased in recent years. Ledalab is one such system that automatically identifies SCRs and is currently considered a gold standard in the field of ambulatory EDA recording. However, Ledalab, like other current systems, cannot distinguish between SCRs and artifacts. The present manuscript describes a novel technique to accurately and efficiently identify SCRs and artifacts using curve fitting and sparse recovery methods We show that our novel approach, when applied to expertly labeled EDA data, detected 69% of the total labeled SCRs in an EDA signal compared to 45% detection ability of Ledalab. Additionally, we demonstrate that our system can distinguish between artifact and SCR shapes with an accuracy of 74%. This work, along with our previous work [3], suggests that matching pursuit is a viable methodology to quickly and accurately identify SCRs in ambulatory collected EDA data, and that artifact shapes can be separated from SCR shapes.

Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms. Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0–10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness. Exercise reduced CIPN symptoms of hot/coldness in hands/feet (−0.46 units, p = 0.045) and numbness and tingling (− 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076). Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients. Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Allostery pervades macromolecular function and drives cooperative binding of ligands to macromolecules. To decipher the mechanisms of cooperative ligand binding it is necessary to define at a microscopic level the structural and thermodynamic consequences of binding of each ligand to its allosterically coupled site(s). However, dynamic sampling of alternative conformations (microstates) in allosteric molecules complicates interpretation of both structural and thermodynamic data. Isothermal titration calorimetry has the potential to directly quantify the thermodynamics of allosteric interactions, but usually falls short of enabling mechanistic insight. This is because 1) its measurements reflect the sum of overlapping caloric processes involving binding-linked population shifts within and between microstates, and 2) data are generally fit with phenomenological binding polynomials that are underdetermined. Nevertheless, temperature-dependent binding data have the potential to resolve overlapping thermodynamic processes, while mechanistically constrained models enable hypothesis testing and identification of informative parameters. We globally fit temperature-dependent isothermal titration calorimetry data for binding of 11 tryptophan ligands to the homo-undecameric trp RNA-binding Attenuation Protein from Bacillus stearothermophilus using nearest-neighbor statistical thermodynamic models. This approach allowed us to distinguish alternative nearest-neighbor interaction models, and quantifies the thermodynamic contribution of neighboring ligands to individual binding sites. We also perform conventional Hill equation modeling and illustrate how comparatively limited it is in quantitative or mechanistic value. This work illustrates the potential of mechanistically constrained global fitting of binding data to yield the microscopic thermodynamic parameters essential for deciphering mechanisms of cooperativity in a wide range of ligand-regulated homo-oligomeric assemblies.

Purpose Cancer-related cognitive impairment is an important problem for patients with breast cancer, yet its trajectory is not fully understood. Some previous cancer-related cognitive impairment research is limited by heterogeneous populations, small samples, lack of prechemotherapy and longitudinal assessments, use of normative data, and lack of generalizability. We addressed these limitations in a large prospective, longitudinal, nationwide study. Patients and Methods Patients with breast cancer from community oncology clinics and age-matched noncancer controls completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) at prechemotherapy and postchemotherapy and at a 6-month follow-up as an a priori exploratory aim. Longitudinal models compared FACT-Cog scores between patients and controls at the three assessments and adjusted for age, education, race, menopausal status, and baseline reading ability, anxiety, and depressive symptoms. A minimal clinically important difference cutoff determined percentages of impairment over time. Results Of patients, 581 patients with breast cancer (mean age, 53 years; 48% anthracycline-based regimens) and 364 controls (mean age, 53 years) were assessed. Patients reported significantly greater cognitive difficulties on the FACT-Cog total score and four subscales from prechemotherapy to postchemotherapy compared with controls as well as from prechemotherapy to 6-month follow-up (all P < .001). Increased baseline anxiety, depression, and decreased cognitive reserve were significantly associated with lower FACT-Cog total scores. Treatment regimen, hormone, or radiation therapy was not significantly associated with FACT-Cog total scores in patients from postchemotherapy to 6-month follow-up. Patients were more likely to report a clinically significant decline in self-reported cognitive function than were controls from prechemotherapy to postchemotherapy (45.2% v 10.4%) and from prechemotherapy to 6-month follow-up (36.5% v 13.6%). Conclusion Patients with breast cancer who were treated in community oncology clinics report substantially more cognitive difficulties up to 6 months after treatment with chemotherapy than do age-matched noncancer controls.

While cognitive-behavioral therapy for insomnia (CBT-I) has been shown to be efficacious in treating cancer survivors' insomnia, 30-60% of individuals have difficulty adhering to intervention components. Psychosocial predictors of adherence and response to CBT-I, such as social support, have not been examined in intervention studies for cancer survivors.Data from a randomized placebo-controlled 2 x 2 trial of CBT-I and armodafinil (a wakefulness promoting agent) were used to assess adherence. Ninety-six cancer survivors participated in the trial (mean age 56, 86% female, 68% breast cancer).CBT-I and armodafinil were administered over the course of seven weeks, and participants were assessed at baseline, during intervention, postintervention, and at a three-month follow-up. Social support was assessed using a Functional Assessment of Chronic Illness Therapy subscale, insomnia severity was assessed using the Insomnia Severity Index, and adherence was measured based on CBT-I sleep prescriptions.At baseline, social support was negatively correlated with insomnia severity (r = -0.30, p = 0.002) and associations between social support, CBT-I, and insomnia were maintained through the three-month follow-up. Social support was positively associated with adherence to CBT-I during intervention weeks 3, 4, and 5, and with overall intervention adherence. At postintervention, both social support and treatment with CBT-I independently predicted decreased insomnia severity (p0.01) when controlling for baseline insomnia severity.Higher social support is associated with better intervention adherence and improved sleep independent of CBT-I. Additional research is needed to determine whether social support can be leveraged to improve adherence and response to CBT-I.

Introduction Abnormal interoception is believed to contribute to anxiety disorders as well as possibly to Insomnia Disorder. We therefore hypothesized that interoceptive sensitivity in persons with Generalized Anxiety Disorder (GAD) would vary with sleep quality and would differ between GAD patients with and without insomnia. Methods 29 subjects (86% female) who reported GAD-7 scores ≥ 10 underwent psychiatric and sleep-disorders interviews and met DSM-5 criteria for GAD. Participants were assigned into an insomnia group if the Insomnia Severity Index (ISI) score exceeded 12 (N=18) or a non-insomnia group if ISI score < 11 (N=11). Participants completed approximately 2 weeks of actigraphy and sleep diaries (mean=14.09 days; SD=4.85) as well as online surveys of sleep quality including the Pittsburg Sleep Quality Index (PSQI) and interoceptive sensitivity including the Multidimensional Assessment of Interoceptive Awareness, the somatic anxiety scale of the State-Trait Inventory for Cognitive and Somatic Anxiety-Trait (STICSA-T) and the Anxiety Sensitivity Index. In addition, 28 participants underwent the Schandry heartbeat-counting task, an objective measure of interoceptive sensitivity. Results GAD-7 scores did not differ between insomnia and non-insomnia groups (t(18.36)=0.074, p = 0.941). However, insomniacs reported significantly higher scores on the somatic anxiety scale of the STICSA than non-insomniacs (t(17.71)=2.094, p=0.051). STICSA-T somatic anxiety scores positively correlated with greater PSQI scores (R=0.588; p=0.002) and trended negatively with actigraphy sleep-efficiency (R = -0.384; p=0.085). Non-insomniacs outperformed insomniacs in the Schandry task (t(25.9)=2.21, p=0.036). Higher Schandry scores were positively correlated with greater total sleep time (R=0.515; p=0.014) and lower ISI scores (R= -0.387; p=0.042). Conclusion Results suggest that GAD patients with insomnia have lesser objective interoceptive sensitivity and more subjective somatic anxiety than those without insomnia. Greater somatic anxiety predicted poorer subjective and objective sleep quality. Hence interoceptive sensitivity may vary with sleep disturbance in GAD. Support R21MH115279

A growing body of research claims that stimuli presented outside conscious awareness can influence affect, speech perception, decision-making, eating behavior, and social judgments. However, research has shown that conscious awareness is a continuous phenomenon. Using a continuous flash suppression (CFS) paradigm to suppress awareness of affective faces (smiling and scowling), we demonstrate that some awareness of suppressed stimuli is required for the stimuli to influence social judgments. We discovered this using a rigorous within-participants psychophysics method that allowed us to assess awareness at very low levels, which is difficult using traditional methods. Our findings place boundary conditions on claims (made previously by us and others) that stimuli presented completely outside conscious awareness influence judgments. This work contributes to the literature highlighting the need to study conscious awareness as a continuous phenomenon and provides a framework for researchers to ask and answer questions regarding conscious awareness and its relation to judgment and behavior.

Commercially available consumer electronics (smartwatches and wearable biosensors) are increasingly enabling acquisition of peripheral physiological and physical activity data inside and outside of laboratory settings. However, there is scant literature available for selecting and assessing the suitability of these novel devices for scientific use. To overcome this limitation, the current paper offers a framework to aid researchers in choosing and evaluating wearable technologies for use in empirical research. Our seven-step framework includes: (1) identifying signals of interest; (2) characterizing intended use cases; (3) identifying study-specific pragmatic needs; (4) selecting devices for evaluation; (5) establishing an assessment procedure; (6) performing qualitative and quantitative analyses on resulting data; and, if desired, (7) conducting power analyses to determine sample size needed to more rigorously compare performance across devices. We illustrate the application of the framework by comparing electrodermal, cardiovascular, and accelerometry data from a variety of commercial wireless sensors (Affectiva Q, Empatica E3, Empatica E4, Actiwave Cardio, Shimmer) relative to a well-validated, wired Mindware laboratory system. Our evaluations are performed in two studies (N=10, N=11) involving psychometrically sound, standardized tasks that include physical activity and affect induction. After applying our framework to this data, we conclude that only some commercially available consumer devices for physiological measurement are capable of wirelessly measuring peripheral physiological and physical activity data of sufficient quality for scientific use cases. Thus, the framework appears to be beneficial at suggesting steps for conducting more systematic, transparent, and rigorous evaluations of mobile physiological devices prior to deployment in studies.

Although recent scientific advances have improved our understanding of basic biological mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN), few interventions are available to prevent or treat CIPN. Although some biological targets from preclinical studies show promise in nonhuman animal models, few targets have been translated to successful clinical trials. To address this problem, the National Cancer Institute’s Symptom Management and Health-Related Quality of Life Steering Committee convened a meeting of experts in the CIPN and oncology symptom management fields to participate in a Clinical Trials Planning Meeting (CTPM). Investigators presented data from preclinical and translational studies for possible CIPN interventions; these were evaluated for readiness of randomized clinical trial testing by experts, and recommendations were provided. Breakout sessions were convened to discuss and develop future studies. The CTPM experts concluded that there is compelling evidence to move forward with selected pharmacological and nonpharmacological clinical trials for the prevention and treatment of CIPN. Several key feasibility issues need to be addressed, however. These include identification of optimal outcome measures to define the CIPN phenotype, establishment of parameters that guide the evaluation of clinically meaningful effects, and adoption of approaches for inclusion of translational and biomarker and/or genetic measures. The results of the CTPM provide support for conducting clinical trials that include both pharmacological and nonpharmacological approaches, alone or in combination, with biomarkers, genetics, or other measures designed to inform underlying CIPN mechanisms. Several working groups were formed to design rigorous CIPN clinical trials, the results of which are ongoing.

Cancer-related fatigue is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, depression and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition and nutritional deficiencies that potentially weaken the cancer survivor and impact cancer-related fatigue. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating cancer-related fatigue. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to cancer-related fatigue. Dietary intake prior to, during and after cancer treatment appears to affect fatigue levels. Increased protein intake may help preserve lean mass and body composition. Dietary patterns that reduce inflammation, such as the Mediterranean diet and other plant-based diets, appear tolerable to cancer survivors and may reduce fatigue. Supplementation with ginseng, ginger or probiotics may improve cancer survivors’ energy levels. Nutritional interventions, alone or in combination with other interventions should be considered as therapy for fatigue in cancer survivors.

OBJECTIVES: Cancer-related fatigue is characterized by an overwhelming sense of tiredness that cannot be relieved by sleep or rest; it often persists for years into survivorship. Maintaining appropriate nutritional status is critical during cancer treatment, though few studies have assessed relationships between diet quality and cancer-related fatigue. Herein, we aimed to investigate the association between serum lycopene, a proxy for diet quality, and fatigue in a large representative sample of the US population. METHODS: Data were obtained from the 2005–2006 NHANES dataset. Serum total lycopene was quantified from fasting blood samples and used as a continuous variable. Patient-reported fatigue was assessed from a question on the validated Patient Health Questionnaire-9: “Over the last 2 weeks, how often have you been bothered by… feeling tired or having little energy?”; fatigue was categorized as no fatigue (0), low fatigue (1), or moderate-severe fatigue (2–3). Multinomial regression models were applied to assess the association between serum lycopene and fatigue while controlling for age, race/ethnicity, and body mass index. Results are reported as odds ratios (OR) and 95% confidence intervals (CIs) for having low or moderate-severe vs. no fatigue for a 10-μg/dL increase in serum lycopene for all participants and those with a previous cancer diagnosis. RESULTS: Participants (n = 4091) were 48.3 ± 18.7 years old, 52% female, and 51.7% non-Hispanic White; 329 had a prior cancer diagnosis. A self-reported cancer diagnosis was associated with a 31.8% greater odds of having moderate-severe vs. no fatigue (OR = 1.32, 95% CI = 1.12–1.55) and a 6.8% greater odds of having low fatigue (OR = 1.07, 95% CI = 0.93–1.22). A 10-μg/dl increase in serum lycopene concentrations was associated with a 5.3% lower odds of moderate-severe vs. no fatigue (OR = 0.95, 95% CI = 0.90–0.99) and a similar odds of low fatigue (OR = 1.01, 95% CI = 0.97–1.04). These associations were similar for patients who had had a cancer diagnosis. CONCLUSIONS: Higher levels of serum lycopene were associated with lower odds of moderate-severe. Dietary interventions should be further explored for their associations with cancer-related fatigue among patients with cancer and cancer survivors. FUNDING SOURCES: National Cancer Institute.

12017 Background: Patients commonly experience impaired sleep throughout cancer treatment and for years into survivorship. Impaired sleep may mediate other cancer-related symptoms and can lead to the inability to complete daily activities and lower quality of life. More effective non-pharmacological treatment options for impaired sleep are needed. We conducted a nationwide, multicenter, phase III randomized controlled trial (RCT) comparing the effects of yoga (Yoga for Cancer Survivors; YOCAS), cognitive behavioral therapy for insomnia (CBT-I), and a behavioral placebo on impaired sleep in cancer survivors. Methods: This RCT was conducted via the URCC NCORP Research Base. Participants were cancer survivors 2-60 months post-treatment with insomnia. They were randomized to 1) YOCAS (75-min session biweekly for 4 wks), 2) CBT-I (90-min session weekly for 8 wks), and 3) behavioral placebo (survivorship health education per ASCO guidelines; 75-min session biweekly for 4 wks). Sleep efficiency, sleep duration, wake after sleep onset (WASO), and sleep latency were assessed via actigraphy at baseline and post-intervention. Actigraphs were worn on the non-dominant wrist 24 hours a day for 7 days. Linear mixed models were used to assess intervention effects on sleep outcomes. Results: 740 survivors were enrolled (93% female, mean age 56±11 years, 73% breast cancer). Results revealed significant group differences among survivors in the 3 arms in sleep efficiency, sleep duration, and WASO (all p0.05). YOCAS and CBT-I subjects maintained sleep efficiency (mean change= -0.8% and -0.03%, respectively, all p>0.05) while behavioral placebo subjects significantly reduced sleep efficiency (mean change= -3.4%, p0.05) while CBT-I and behavioral placebo subjects significantly reduced sleep duration (mean change= -20.3 minutes and -26.6 minutes, respectively, all p

e24095 Background: Over half of patients receiving neurotoxic taxane, platinum, or bortezomib chemotherapy experience CIPN—a dose-limiting toxicity involving numbness and pain in the extremities. There are limited biomarkers and treatments for CIPN partly due to lack of knowledge of its pathophysiology. Here, we studied whether CIPN involves changes in the brain’s sensory processing circuitry to inform novel brain-based biomarkers and brain-based treatments for CIPN. Methods: Eleven patients scheduled to receive taxane, platinum, or bortezomib rated CIPN severity (CIPN-20) and completed an fMRI scan before starting neurotoxic chemotherapy and/or 12 weeks later. The 7-min fMRI task involved alternating 20-sec trials of distinct attentional focus: (1) their left fingertips (somatosensory attention), (2) their heart (interoceptive attention), and (3) a flashing word “target” (visual attention; the reference condition). We found an activation cluster in primary somatosensory cortex (S1) comparing somatosensory vs. visual attention and another cluster in primary interoceptive cortex (mid/posterior insula) comparing interoceptive vs. visual attention. We tested for associations between CIPN severity and task-based activations in S1 and the insula. Because this is a pilot study, we present effect sizes (ESs) using Cohen’s d and Pearson’s r, not p-values. Results: The 11 patients were 63±12 years old, 54% women, and 54% had breast cancer with high-quality fMRI data (16 scans; 8 pre-chemotherapy). As expected, somatosensory attention increased activation in S1 compared to visual attention (ES = 1.46), and interoceptive attention increased activation in the insula compared to visual attention (ES = 0.94). Patients with worse CIPN had smaller increases in S1 activation during somatosensory vs. visual attention (ES = 0.38), suggesting reduced S1 activation during somatosensory attention (i.e., failure to activate S1) and/or increased S1 activation during visual attention (i.e., S1 chronically activated). Similarly, patients with worse CIPN had smaller increases in insula activation during interoceptive vs. visual attention (ES = 0.57). Individual differences in S1 or insula activity were not significantly explained by age, anxiety, or problems remembering (all ESs < 0.12). Conclusions: CIPN severity was associated with changes in brain activity during a simple attentional task during fMRI scanning, implicating the brain’s somatosensory and interoceptive processing in CIPN. Future work should test for replication and develop biomarkers and treatments for CIPN that target somatosensory and interoceptive processing, perhaps using this attention task. NCT03021174. Funding: NIH R25CA102618, UG1CA189961, K07CA221931. Clinical trial information: NCT03021174.

12114 Background: In a nationwide prospective study, we found that patients with breast cancer had greater perceived cognitive impairment (PCI) before and after chemotherapy compared to controls without cancer. To gain further insight into the role that inflammation plays in cognitive function, we evaluated relationships between immune cell counts and lymphocyte:monocyte ratio with PCI at pre- and post- chemotherapy. Methods: Data were collected as part of longitudinal cohort study conducted through the National Cancer Institute Community Oncology Research Program network (NCT01382082). Self-reported PCI was scored at pre-chemotherapy (0-7 days before first chemotherapy) and post-chemotherapy (0-30 days after last chemotherapy) from the PCI sub-scale of the Functional Assessment of Cancer Therapy: Cognitive Function (possible score range 0-72). Immune cell counts were measured by complete blood count with differential at pre- and post- chemotherapy. Lymphocyte:monocyte ratio (LMR) was calculated. Separate linear regression models evaluated the association of immune cell counts and LMR with 1) pre-chemotherapy PCI and 2) post-chemotherapy PCI. Models were adjusted for age, cognitive reserve (reading score), anxiety, and depression. Results: PCI and immune cell data were available for 544 patients at pre-chemotherapy and 532 at post-chemotherapy. Subjects had a mean age of 53.1 (SD=10.8). At pre-chemotherapy, higher basophil count and higher LMR were significantly associated with worse PCI (β=5.73, SE=2.37, p

12109 Background: Cancer-related fatigue is a common, debilitating condition that can persist for months or years after cancer treatment. Time-restricted eating has been shown to improve circadian rhythm and strengthen rest and activity patterns, and therefore could help reduce persistent fatigue. Herein, we evaluated the feasibility of recruiting cancer survivors to a two-week, single-arm, time-restricted eating intervention with a 10-h eating window, assessed safety of the intervention, monitored adherence, and obtained initial estimates of within-group change in patient-reported fatigue. Methods: We recruited adults 4-60 months post-cancer treatment who had a fatigue level ≥3 on a scale from 0-10 and who did not already consume food within a 10-h window. Participants were asked to consume all food and beverages within a self-selected 10-h eating window for 14 days; water was allowed at all times. Participants completed a daily diary indicating when they began and stopped eating each day. To assess fatigue, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Brief Fatigue Inventory (BFI) at pre- and post-intervention. We report mean±standard deviation and used a t-test to assess differences in pre- vs. post-intervention scores. Results: A total of 21 participants consented (20 breast cancer, 1 prostate cancer; 20 female; age 57.7±11.4 years; 1.6±1.1 years post-primary treatment). The study was feasible: 19/21 (90.5%) completed pre- and post-intervention assessments and daily diaries. It was also safe: there were two mild adverse events—one unlikely (insomnia) and one possibly related to the intervention (acute headache) and no severe adverse events. Most of the participants adhered to the intervention; 14/19 (73.7%) ate all of their food within a 10-h window at least 80% of the days, and 16/19 (84.2%) reported an average eating window ≤10 h. Fatigue scores improved a clinically meaningful degree for FACIT-F total score, FACIT-F fatigue subscale, and the BFI total score from pre- to post-intervention per established cutoffs (Table). Conclusions: Cancer survivors were willing and able to adhere to a two-week time-restricted eating intervention, and the intervention was safe. Also, fatigue was reduced with moderate to large effect sizes after two weeks of time-restricted eating. Based on our results, a follow-up randomized controlled trial to investigate time-restricted eating to alleviate cancer-related fatigue among cancer survivors is indicated. Funding: NIH/NCI UG1CA189961, T32CA102618. Clinical trial information: NCT04243512. [Table: see text]

Before treatment, cancer patients need information about side effects and prognosis, while after treatment they need information to transition to survivorship. Research documenting these needs is limited, especially among racial and ethnic minorities. This study evaluated cancer patients’ needs according to race both before and after treatment. We compared white (n = 904) to black (n = 52) patients receiving treatment at 17 National Cancer Institute Community Oncology Research Program (NCORP) sites on their cancer-related concerns and need for information before and after cancer treatment. Two-sample t test and chi-squared analyses were used to assess group differences. Compared to white patients, black patients reported significantly higher concerns about diet (44.3 vs. 25.4 %,) and exercise (40.4 vs. 19.7 %,) during the course of treatment. Compared to whites, blacks also had significantly higher concern about treatment-related issues (white vs. black mean, 25.52 vs. 31.78), self-image issues (7.03 vs. 8.60), family-related issues (10.44 vs. 12.84), and financial concerns (6.42 vs. 8.90, all p < 0.05). Blacks, compared to whites, also had significantly greater post-treatment information needs regarding follow-up tests (8.17 vs. 9.44), stress management (4.12 vs. 4.89), and handling stigma after cancer treatment (4.21 vs. 4.89) [all p < 0.05]. Pre-treatment concerns and post-treatment information needs differed by race, with black patients reporting greater information needs and concerns. In clinical practice, tailored approaches may work particularly well in addressing the needs and concerns of black patients.

12040 Background: Older patients with advanced cancer often have comorbidities that increase the risk of toxicity from neoplastic therapy but are not always considered in treatment planning. We assessed the utility of a geriatric assessment (GA) intervention to increase the number and quality of discussions about comorbidities among oncologists, older patients, and caregivers. Methods: This multi-site trial enrolled patients who were ≥70 years, had advanced solid tumors or lymphoma, had ≥1 GA impairment, and who were considering or receiving cancer treatment. All patients received the GA and completed an Older Americans Resources and Services Comorbidity survey, which evaluated 15 conditions and interference with activities (clinical impairment = ≥3 comorbidities or ≥1 highly interfering). Oncology practices were randomized to intervention (GA with a summary with management recommendations provided to oncologists) or usual care (GA only). The clinic visit after GA was audio-recorded, transcribed, and coded for GA topics including comorbidity. Generalized linear mixed models adjusting for site (random effect) were used to assess the effect of the intervention. Results: Patients (n=527 evaluable, 76.6±5.2 years, 49% female) and oncologists (n=131, 63 in intervention) were enrolled from 31 sites. In total, 94.5% of patients had ≥1 comorbidity with an average of 3.2±1.9; 64% were clinically impaired by comorbidity (p=0.76 between arms). The intervention arm had twice the number of conversations about comorbidities (1.02 vs. 0.52 conversations per patient, difference 0.50, 95% CI 0.18-0.81, p=0.004) and conversations were more likely to be initiated by the oncologist (p