Digitizing Survivorship Care Plans Through the POST-Treatment Health Outcomes of Cancer Survivors (POSTHOC) Mobile App: Protocol for a Phase II Randomized Controlled Trial.

BACKGROUND: Survivorship care plans (SCPs) are provided at the completion of cancer treatment to aid in the transition from active treatment to long-term survivorship. They describe the details of a patient's diagnosis and treatment and offer recommendations for follow-up appointments, referrals, and healthy behaviors. The plans are currently paper-based and become outdated as soon as a patient's health status changes. There is a need to digitize these plans to improve their accessibility, modifiability, and longevity. With current technology, SCPs can be linked to mobile devices and activity trackers so that patients can track health behaviors and compare them to their clinical goals, taking charge of their own health. OBJECTIVE: A mobile app, POSTHOC (POST-Treatment Health Outcomes of Cancer Survivors), that digitizes the SCP was developed, with goals of integrating it with wearable technologies and electronic medical records. Herein, we are conducting a randomized controlled trial that evaluates the POSTHOC app versus the traditional SCP on total symptom burden in the early posttreatment period. METHODS: We will recruit 54 patients who have recently completed curative therapy for cancer (any type) in person and remotely. They will be randomized 2:1, POSTHOC:usual care (unblinded). Those randomized to the POSTHOC group will receive their SCP via the app and will choose to focus on nutrition or exercise for the duration of the study based on their individual plan and personal preferences. Those randomized to the control group will get a paper-based plan. At baseline, 6 weeks, and 12 weeks, we will evaluate patient-reported outcomes, including total symptom burden (web-based questionnaire), diet (24-hour Automated Self-Administered [ASA24]), and physical activity (Fitbit Charge 6 [Google LLC]). We will also collect quantitative and qualitative feedback on the usability of the app from those in the POSTHOC arm to improve the app for future implementation studies, with a specific focus on patient-provider communication. For feasibility, we will calculate the percentage of patients who used the POSTHOC app at least 3 times per week. We will use linear mixed models to evaluate the effects of the POSTHOC app versus those of usual care on other outcomes at weeks 6 and 12. RESULTS: This trial is open to accrual in the University of Maryland Medical System as of March 2024, and as of July 3, 2024, a total of 20 participants have consented. CONCLUSIONS: This study is among the first to digitize the SCP in a mobile app and test the effects of a mobile health-delivered behavioral health intervention on symptom burden in cancer survivors. Our results will provide evidence about the effects of health self-management on symptoms. This knowledge will be integral to larger randomized controlled studies, integration with the electronic medical record, and nationwide implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05499663; https://clinicaltrials.gov/ct2/show/NCT05499663. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59222.

Dietary Counseling Interventions During Radiation Therapy: A Systematic Review of Feasibility, Safety, and Efficacy.

Radiotherapy is a common cancer treatment, and concurrent nutritional interventions can maintain nutritional status and improve clinical and supportive care outcomes. However, optimal nutritional interventions during radiotherapy are not firmly established. Herein, we assessed the feasibility, safety, and efficacy of dietary counseling interventions without oral nutrition supplements on health outcomes in adults receiving radiotherapy for cancer in a systematic review. Prospective clinical trials that implemented nutritional counseling interventions during radiotherapy were identified from four databases from inception through December 2023. Feasibility, safety, and efficacy were extracted from 32 articles that described 23 randomized and 4 non-randomized clinical trials. The interventions included individualized nutritional counseling (n = 14 articles), nutritional counseling plus exercise (n = 4), and nutritional counseling focused on increasing or reducing intake of specific nutrients (n = 9). Trials targeted head and neck (n = 12), pelvic cancers (n = 14), and/or breast (n = 5) cancers. Control groups had variable designs and included general nutrition education and intervention as needed. Studies recruited 120 ± 104 participants (range 26-468). Interventions tended to be feasible regarding retention and attendance at sessions, though feasibility metrics varied among different interventions. Most interventions were safe with no studies reporting adverse events attributable to dietary intervention. Individualized dietary counseling interventions tended to lead to between-group differences favoring the intervention group in regard to improved nutritional status, maintenance or attenuation of loss of body mass, improved quality of life, and reduced radiation-induced toxicities. Diets that encouraged/discouraged specific nutrients tended to recruit patients receiving radiation to the pelvic area and resulted in positive or neutral effects on gastrointestinal symptoms. In conclusion, nutritional interventions appear to be feasible, safe, and effective during radiotherapy for various symptom outcomes.

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

PURPOSE: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. METHODS: Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. RESULTS: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: - 7.9 ± 5.7, effect size [ES] = - 0.9 at mid-intervention; - 4.8 ± 7.3, ES = - 0.5 at post-intervention), CIPN signs (ES = - 1.0 and - 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2 = 40-60%) and higher functional connectivity within the salience network (R2 = 20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). CONCLUSION: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. TRIAL REGISTRATION: Registered Jan 2017 on ClinicalTrials.gov as NCT03021174.

Barriers and Facilitators for Participation in Brain Magnetic Resonance Imaging (MRI) Scans in Cancer Research: A Feasibility and Acceptability Analysis.

Purpose: A growing body of research suggests that the brain is implicated in cognitive impairment, fatigue, neuropathy, pain, nausea, sleep disturbances, distress, and other prevalent and burdensome symptoms of cancer and its treatments. Despite anecdotal evidence of difficulties using gold-standard magnetic resonance imaging (MRI) to study the brain, no studies have systematically reported reasons that patients with cancer do or do not complete research MRI scans, making it difficult to understand the role of the brain related to these symptoms. The goal of this study was to investigate these reasons and to suggest possible solutions. Methods: We analyzed data from 72 patients with cancer (mostly breast and gastrointestinal) from 3 studies: MRI was mandatory in Study 1; MRI was optional in Studies 2-3. Patients provided reasons for completing or not completing optional research MRI scans. Results: The percentage of scans completed when MRI was mandatory was 76%, and when optional, it was 36%. The most common reasons for not completing optional scans were claustrophobia (40%), safety contraindications (11%), discomfort (5%), a busy MRI schedule (5%), and the scanner being too far away (4%). Older patients were more likely to complete at least one scan (log(odds) = 0.09/year, p = 0.02). Conclusion: Although brain MRI is feasible for many patients with cancer, it can be difficult or not feasible for patients with claustrophobia, safety issues, busy schedules, or transportation issues. Improving communication, comfort, and access to a scanner may help. Reducing inequities related to study participation can improve research supportive care research.

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Methods: Nineteen patients (65±11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. Results: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: -7.9±5.7, effect size [ES]=-0.9 at mid-intervention; -4.8±7.3, -ES=0.5 at post-intervention), CIPN signs (ES=-1.0 and -0.1), and physical function (ES=0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2=40-60%) and higher functional connectivity within the salience network (R2=20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). Conclusion: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. ClinicalTrials.gov identifier NCT03021174.

Fear-related psychophysiological patterns are situation and individual dependent: A Bayesian model comparison approach.

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 across situations and/or individuals performed much worse by comparison. These results call into question the assumption of generalizability of autonomic-subjective mappings across instances of fear, as required in translational research from nonhuman animals to humans, and advance a situated approach to understanding the autonomic correlates of fear experience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preliminary evaluation of novel Bodily Attention Task to assess the role of the brain in chemotherapy-induced peripheral neurotoxicity (CIPN).

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, sometimes dose-limiting side effect of neurotoxic chemotherapy. Treatment is limited because its pathophysiology is poorly understood. Compared to research on peripheral mechanisms, the role of the brain in CIPN is understudied and it may be important to develop better treatments. We propose a novel task that assesses brain activation associated with attention to bodily sensations (interoception), without the use of painful stimulation, to understand how CIPN symptoms may be processed in the brain. The goals of this preliminary study were to assess, 1) feasibility of the task, 2) sensitivity to changes in brain activity, and 3) suitability for assessing relationships between brain activation and CIPN severity. Eleven participants with varying types of cancer completed a brain fMRI scan and rated CIPN severity (CIPN-20) before and/or 12 weeks after starting neurotoxic chemotherapy. The Bodily Attention Task is a 7.5-min long fMRI task involving attentional focus on the left fingertips, the heart, or a flashing word "target" for visual attention (reference condition). Feasibility was confirmed, as 73% of all data collected were usable and participants reported feeling or focus during 75% of the trials. Regarding brain activity, finger attention increased activation in somatosensory regions (primary sensory cortex, insula) and sensory integration regions (precuneus, dorsolateral prefrontal cortex). Exploratory analyses suggested that brain activation may be associated with CIPN severity. A larger sample size and accounting of confounding factors is needed to test for replication and to identify brain and interoceptive biomarkers to help improve the prediction, prevention, and treatment of CIPN.

Adaptive thresholding increases sensitivity to detect changes in the rate of skin conductance responses to psychologically arousing stimuli in both laboratory and ambulatory settings.

Psychophysiologists recording electrodermal activity (EDA) often derive measures of slow, tonic activity-skin conductance level (SCL)-and faster, more punctate changes-skin conductance responses (SCRs). A SCR is conventionally considered to have occurred when the local amplitude of the EDA signal exceeds a researcher-determined threshold (e.g., 0.05 µS), typically fixed across study participants and conditions. However, fixed SCR thresholds can preferentially exclude data from individuals with low SCL because their SCRs are smaller on average, thereby reducing statistical power for group-level analyses. Thus, we developed a fixed plus adaptive (FA) thresholding method that adjusts identification of SCRs based on an individual's SC at the onset of the SCR to increase statistical power and include data from more participants. We assess the utility of applying FA thresholding across two independent samples and explore age and race-related associations with EDA outcomes. Study 1 uses wired EDA measurements from 254 healthy adults responding to evocative images and sounds in a laboratory setting. Study 2 uses wireless EDA measurements from 20 children with autism in a clinical environment while they completed behavioral tasks. Compared to a 0.01, 0.03, and 0.05 µS fixed threshold, FA thresholding at 1.9% modestly increases statistical power to detect a difference in SCR rate between tasks with higher vs. lower subjective arousal and reduces exclusion of participants by up to 5% across both samples. This novel method expands the EDA analytical toolbox and may be useful in populations with highly variable basal SCL or when comparing groups with different basal SCL. Future research should test for reproducibility and generalizability in other tasks, samples, and contexts. IMPACT STATEMENTS: This article is important because it introduces a novel method to enhance sensitivity and statistical power in analyses of skin conductance responses from electrodermal data.

Dietary Composition, Meal Timing, and Cancer-Related Fatigue: Insights From the Women's Healthy Eating and Living Study.

BACKGROUND: Cancer-related fatigue is difficult to treat, and dietary interventions are promising yet underused. OBJECTIVE: We explored associations between dietary patterns and fatigue, and the effect of a dietary intervention versus control on fatigue using Women's Healthy Eating and Living study data, plus mediators and moderators of the intervention effect. METHODS: The Women's Healthy Eating and Living study was a randomized controlled trial among early-stage breast cancer survivors. The 4-year intervention encouraged fruits, vegetables, fiber, and 15% to 20% calories from fat. Fatigue outcomes included a 9-item energy scale and a single-item tiredness question. Dietary quality was estimated using a modified Healthy Eating Index (24-hour dietary recall) and serum carotenoid concentrations. Nutrient timing was obtained from 4-day food logs. RESULTS: Among 2914 total participants, lower body mass index was associated with less tiredness and more energy at baseline (P < .001 for both). Earlier start and end times for daily eating windows were associated with less tiredness (P = .014 and P = .027, respectively) and greater energy (P = .006 and P = .102, respectively). The intervention did not lead to improvements in fatigue on average (P > .125). However, the intervention was more effective for participants who were younger, had fewer comorbidities, and did not have radiation treatment. Mediators included increases in serum carotenoids, increases in the modified Healthy Eating Index, and weight loss/maintenance. CONCLUSION: Diet quality and earlier eating windows were associated with less fatigue. IMPLICATIONS FOR PRACTICE: Programs that encourage high diet quality and a morning meal and discourage nighttime eating should be tested for efficacy in reducing cancer-related fatigue in survivorship.

Updated systematic review of the effects of exercise on understudied health outcomes in cancer survivors.

INTRODUCTION: The American College of Sports Medicine provided guidelines for exercise prescriptions in cancer survivors for specific cancer- and treatment-related health outcomes. However, there was insufficient evidence to generate exercise prescriptions for 10 health outcomes of cancer treatment. We sought to update the state of evidence. METHODS: We conducted a systematic review of these 10 understudied health outcomes (bone health, sleep, cardiovascular function, chemotherapy-induced peripheral neuropathy (CIPN), cognitive function, falls and balance, nausea, pain, sexual function, and treatment tolerance) and provided an update of evidence. RESULTS: While the evidence base for each outcome has increased, there remains insufficient evidence to generate exercise prescriptions. Common limitations observed across outcomes included: variability in type and quality of outcome measurement tools, variability in definitions of the health outcomes, a lack of phase III trials, and a majority of trials investigating breast or prostate cancer survivors only. CONCLUSION: We identified progress in the field of exercise oncology for several understudied cancer- and treatment-related health outcomes. However, we were not able to generate exercise prescriptions due to continued insufficient evidence base. More work is needed to prescribe exercise as medicine for these understudied health outcomes, and our review highlights several strategies to aid in research acceleration within these areas of exercise oncology.

Chemotherapy-related symptoms and exercise adherence in older patients with myeloid neoplasms.

PURPOSE: Exercise may ameliorate treatment-related symptoms, but older adults have lower exercise adherence compared to their younger counterparts due to treatment-related symptoms. METHODS: We recruited older patients with myeloid neoplasms receiving chemotherapy to a pilot study of a mobile health exercise intervention. Participants entered their steps and resistance data into the app daily, and symptom data twice a week, over an 8-12 week period. In this proof-of-concept analysis, we used a linear mixed-effects model to assess the association of symptoms from the previous week with exercise adherence in the current week among older adults with myeloid neoplasms. RESULTS: Mean age was 74.3 (SD = 5.0) years (N = 7). At baseline, patients on average walked 2564 daily steps (SD = 1816), which increased to 2967 (SD = 3448) post-intervention. Patients on average performed 3.5 (SD = 2.6) days of resistance training weekly, with mean duration of 21.5 min (SD = 11.6) and rated perceived exertion of 3.68 (SD = 1.78) on a 0-10 scale. Lower average steps in the current week was associated with greater interference with daily activities from pain (ß = - 203.13, p = 0.05), memory (ß = - 492.29, p = 0.09), numbness (ß = - 353.57, p = 0.07), and sadness (ß = - 403.03, p = 0.09) in the previous week. Similarly, lower average resistance minutes in the current week were associated with greater pain, sadness, and anxiety in the previous week. CONCLUSIONS: We found that greater pain, sadness, and anxiety were associated with lower exercise adherence. Symptom monitoring and management in older adults with myeloid neoplasms receiving chemotherapy can promote exercise adherence and in turn improve symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04035499. Registered 7/29/2019.

Framework to leverage physical therapists for the assessment and treatment of chemotherapy-induced peripheral neurotoxicity (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.

Serum carotenoids and cancer-related fatigue: An analysis of the 2005-2006 National Health and Nutrition Examination Survey.

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 (NHANES) 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 non-melanoma 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 4091 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-standard deviation 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.

The Effects of a Mediterranean Diet Intervention on Cancer-Related Fatigue for Patients Undergoing Chemotherapy: A Pilot Randomized Controlled Trial.

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 <5 (n = 21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES = −0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p < 0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.

Time-restricted Eating to Address Cancer-related Fatigue among Cancer Survivors: A Single-arm Pilot Study.

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. This study was pre-registered at clinicaltrials.gov in January 2020 (NCT04243512). 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<0.001, effect size [ES]=0.55), 30.6 ± 35.9 points for the FACIT-F total score (p<0.001, ES=0.50), and -1.0 ± 1.7 points on the BFI (p<0.001, ES=-0.58). Conclusion: A 10-h TRE intervention was feasible and safe among survivors, and fatigue improved with a moderate effect size after two weeks. Limitations: This was a single-arm study, so it is possible that expectation effects were present for fatigue outcomes, independent of effects of TRE per se. However, this feasibility trial supports evaluation of TRE in randomized controlled trials to address persistent cancer-related fatigue.

The association between cancer-related fatigue and diabetes from pre-chemotherapy to 6 months post-chemotherapy.

PURPOSE: To quantify the relationship between diabetes and fatigue from pre-chemotherapy to 6 months post-chemotherapy for women with breast cancer compared to women without a history of cancer (controls). METHODS: This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and controls. Diabetes diagnosis (yes/no) was obtained at baseline, and cancer-related fatigue 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. Repeated measures mixed effects models estimated the association between fatigue and diabetes controlling for cancer (yes/no), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education. RESULTS: Among 439 patients and 235 controls (52.8 ± 10.5 years old), diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). At baseline, diabetes was associated with worse fatigue (4.1 ± 1.7 points, p = 0.017). Also, diabetes was associated with clinically meaningful worse fatigue throughout the study period among all participants (5.2 ± 1.9 points, p = 0.008) and patients alone (4.5 ± 2.0, p = 0.023). For the MFSI subdomains among patients, diabetes was associated with worse general (p = 0.005) and mental fatigue (p = 0.026). CONCLUSIONS: Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe cancer-related fatigue in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address cancer-related fatigue during chemotherapy treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01382082, first posted June 27, 2011.

Exploratory Analysis of Associations Between Whole Blood Mitochondrial Gene Expression and Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Cancer-related fatigue is a prevalent, debilitating, and persistent condition. Mitochondrial dysfunction is a putative contributor to cancer-related fatigue, but relationships between mitochondrial function and cancer-related fatigue are not well understood. OBJECTIVES: We investigated the relationships between mitochondrial DNA (mtDNA) gene expression and cancer-related fatigue, as well as the effects of fish and soybean oil supplementation on these relationships. METHODS: A secondary analysis was performed on data from a randomized controlled trial of breast cancer survivors 4-36 months posttreatment with moderate-severe cancer-related fatigue. Participants were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g each daily for 6 weeks. At pre- and postintervention, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and provided whole blood for assessment of mtDNA gene expression. The expression of 12 protein-encoding genes was reduced to a single dimension using principal component analysis for use in regression analysis. Relationships between mtDNA expression and cancer-related fatigue were assessed using linear regression. RESULTS: Among 68 participants, cancer-related fatigue improved and expression of all mtDNA genes decreased over 6 weeks with no effect of treatment group on either outcome. Participants with lower baseline mtDNA gene expression had greater improvements in cancer-related fatigue. No significant associations were observed between mtDNA gene expression and cancer-related fatigue at baseline or changes in mtDNA gene expression and changes in cancer-related fatigue. DISCUSSION: Data from this exploratory study add to the growing literature that mitochondrial dysfunction may contribute to the etiology and pathophysiology of cancer-related fatigue.

Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of neurotoxic antineoplastic agents commonly used to treat cancer. Patients with CIPN experience debilitating signs and symptoms, such as combinations of tingling, numbness, pain, and cramping in the hands and feet that inhibit their daily function. Among the limited prevention and treatment options for CIPN, exercise has emerged as a promising new intervention that has been investigated in approximately two dozen clinical trials to date. As additional studies test and suggest the efficacy of exercise in treating CIPN, it is becoming more critical to develop mechanistic understanding of the effects of exercise in order to tailor it to best treat CIPN symptoms and identify who will benefit most. To address the current lack of clarity around the effect of exercise on CIPN, we reviewed the key potential mechanisms (e.g., neurophysiological and psychosocial factors), mediators (e.g., anti-inflammatory cytokines, self-efficacy, and social support), and moderators (e.g., age, sex, body mass index, physical fitness, exercise dose, exercise adherence, and timing of exercise) that may illuminate the relationship between exercise and CIPN improvement. Our review is based on the studies that tested the use of exercise for patients with CIPN, patients with other types of neuropathies, and healthy adults. The discussion presented herein may be used to (1) guide oncologists in predicting which symptoms are best targeted by specific exercise programs, (2) enable clinicians to tailor exercise prescriptions to patients based on specific characteristics, and (3) inform future research and biomarkers on the relationship between exercise and CIPN.

Inflammation, Attention, and Processing Speed in Patients With Breast Cancer Before and After Chemotherapy.

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 (ß = 0.610, SE = 0.241, P = .01); higher IL-4 (ß = -1.098, SE = 0.516, P = .03) and IL-10 (ß = -0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (ß = 0.841, SE = 0.260, P = .001), sTNFRI (ß = 6.638, SE = 2.208, P = .003), and sTNFRII (ß = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (ß = -1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (ß = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (ß = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (ß = -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.