Cancer-Related Fatigue Outcome Measures in Integrative Oncology: Evidence for Practice and Research Recommendations.

Cancer-related fatigue (CRF) is one of the most common symptoms across the cancer continuum and is often underreported and undertreated. Defined as a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or its treatment, CRF includes physical, emotional, cognitive, and spiritual dimensions. Patient-reported outcome (PRO) measures are the most widely used tool to screen for and assess fatigue and the associated negative impacts on quality of life. However, selecting subjective CRF measures can be complex. This has resulted in the availability of and inconsistent use of numerous PROs, limiting the ability to cross-compare outcomes clinically and within research. To address this, the PROs that are most widely reported in the literature are recommended to support the standardization of a core set of validated measures. The National Comprehensive Cancer Network single-item tool for clinical significance is recommended for quick use in clinical environments; the Brief Fatigue Inventory allows for fast, easy, helpful cutoffs on severity threshold for triage, and measures both severity and interference with daily functioning; while the MD Anderson Symptom Inventory allows for multisymptomatic assessment. In addition, a fundamental consideration for any PRO use is the administrative burden on the patient and clinician. In this review, we aim to summarize current, validated PROs specific to CRF to aid clinicians and researchers in patient care and in study design and implementation. We conclude with suggestions for future directions in CRF research that can increase the possibility for long-term impact on future guidelines of fatigue management.

Acupressure for Cancer-fatigue in Ovarian Cancer Survivor (AcuOva) Study: A community-based clinical trial study protocol examining the impact of self-acupressure on persistent cancer-related fatigue in ovarian cancer survivors.

Background Persistent cancer-related fatigue is one of the most common and burdensome symptoms experienced by ovarian cancer survivors. Despite the high burden of fatigue in ovarian cancer survivors, there are few available treatments. Previous research has shown self-acupressure to be a safe method for improving persistent fatigue, sleep, and quality of life among fatigued breast cancer survivors, yet there are no studies examining self-acupressure for fatigue in ovarian cancer survivors. Methods A three group parallel, randomized controlled trial will be conducted to evaluate the efficacy of self-acupressure taught and delivered via a patient-designed, custom-built mobile app ("MeTime") and accompanying hand-held device ("AcuWand") to help guide correct pressure application. A sample of 165 ovarian cancer survivors, who have completed primary cancer treatment will be recruited from tumor registries in Michigan and Los Angeles. Participants will be mailed a tablet preloaded with the app and a device, and all visits will be conducted remotely. Participants will be randomized to 6-weeks of daily self-acupressure via the app and device, or a sham app and device, or no care group. Self-report measures will be completed at baseline, 6-weeks (post-intervention), 3-, and 6-months. Primary outcome is the Brief Fatigue Inventory; secondary outcomes are sleep, quality of life, and symptoms commonly associated with persistent fatigue. Discussion An app based self-acupressure treatment may be an easily-accessible and inexpensive treatment to reduce fatigue in ovarian cancer survivors. The results of the study will provide information on the possible benefits of app-based self-acupressure for fatigue in ovarian cancer survivors. Trial registration: This study is registered at ClinicalTrials.gov Identifier: NCT03763838, date registered on December 4, 2018.

Pros and Cons of Dietary Strategies Popular Among Cancer Patients.

As many as 48% of cancer patients pursue popular diets, including the alkaline, Paleolithic, ketogenic, vegan, and macrobiotic diets, with the hope that they will improve survival and prevent recurrence. These diets have positive aspects consistent with the dietary guidelines proposed by the American Cancer Society (ACS) and the American Institute for Cancer Research (AICR). All of the diets emphasize eating vegetables, all but the ketogenic diet encourage eating fruit, and all but the vegan diet limit refined grains and alcohol. Both the macrobiotic and the alkaline diets meet the majority of the ACS and AICR guidelines. Negative aspects of these diets include pseudo-scientific rationales for their anti-cancer properties, limited evidence that they improve cancer outcomes, the possibility for nutrient insufficiencies, and elimination of food groups proven beneficial for cancer prevention and general health. Moreover, with nutritional counseling, nutrient insufficiencies and misalignment with cancer clinical guidelines can often be addressed. Clinicians should consider strategies to encourage evidence-based dietary changes that encourage positive features of popular cancer diets, while minimizing negative aspects.

Integrative Oncology Scholars Program: A Model for Integrative Oncology Education.

OBJECTIVES: Oncology providers are often confronted by patients who use complementary or alternative therapies, but have limited knowledge or confidence on how to advise patients on appropriate use. Despite this, there are few opportunities for oncology providers to learn about complementary or alternative therapies, while at the same time there is a high demand for integrative oncology (IO) training. To address a gap in IO educational opportunities, and particularly for nonphysicians, we created the Integrative Oncology Scholars (IOS) Program. The program's goal is to train 100 IO leaders and facilitate partnerships between them and complementary practitioners. DESIGN: Four iterations of a year-long National Cancer Institute-funded educational program that combines in-person team-based learning and eLearning to teach the evidence, application, and philosophy supporting IO. SETTINGS: In-person sessions take place at the University of Michigan, and eLearning is implemented using a Canvas website (Instructure, Inc., Salt Lake City, UT). SUBJECTS: Nurses, social workers, physician assistants, psychologists, physicians, pharmacists, and physical/occupational therapists with active oncology practices. Educational intervention: Four cohorts of 25 oncology providers per year will learn the evidence base for complementary and alternative approaches to a wide number of oncology topics, including symptom control, dietary supplements commonly used by cancer patients, diet, and the utility of specific integrative approaches for common oncology side-effects such as fatigue. OUTCOME MEASURES: A mixed methods approach will be used to evaluate overall IOS Program progress and individual scholar's impact on IO research, education, and clinical endeavors. RESULTS: The first cohort of 25 IOS has been recruited and their education will begin in Summer 2018. Scholars come from 13 states and represent 23 different healthcare systems. CONCLUSIONS: The IOS Program has the potential to increase the number of trained IO providers, educators, and researchers in the United States.

Impact of Self-Acupressure on Co-Occurring Symptoms in Cancer Survivors.

BACKGROUND: Cancer survivors with fatigue often experience depressive symptoms, anxiety, and pain. Previously, we reported that self-acupressure improved fatigue; however, its impact on other co-occurring symptoms and their involvement in treatment action has not been explored. METHODS: Changes in depressive symptoms, anxiety, and pain were examined prior to and following two formulas of self-acupressure and usual care using linear mixed models in 288 women from a previously reported clinical trial. Participants were categorized by random assignment into one of three groups: 1) relaxing acupressure, 2) stimulating acupressure, or 3) usual care. Moderators investigated were body mass index, age, depressive symptoms, anxiety, sleep and pain, and mediators were change in these symptoms. RESULTS: Following treatment, depressive symptoms improved statistically significantly for the relaxing acupressure group (41.5%) compared with stimulating acupressure (25%) and usual care (7.7%). Both acupressure groups were associated with greater improvements in anxiety than usual care, but only relaxing acupressure was associated with greater reductions in pain severity, and only stimulating acupressure was associated with greater reductions in pain interference. There were no statistically significant moderators of sleep quality, anxiety, or depressive symptoms. Fatigue statistically significantly moderated pain, and age statistically significantly modified fatigue. Changes in depressive symptoms and sleep quality statistically significantly mediated the relationship between relaxing acupressure and usual care on fatigue; however, the effect was small. CONCLUSIONS: Acupressure was associated with greater improvements than usual care in anxiety, pain, and symptoms of depression in breast cancer survivors with troublesome fatigue. These findings warrant further evaluation in suitably controlled randomized trials.

Fatigue reduction diet in breast cancer survivors: a pilot randomized clinical trial.

PURPOSE: Fatigue is a prevalent and burdensome effect of breast cancer. Fatigue has been linked to chronic inflammation, and diets high in antioxidant nutrients have been associated with lesser prevalence and severity of fatigue. Studies are needed, however, to test if antioxidant-rich diets could improve fatigue. METHODS: Pilot, randomized, trial conducted between January 2014 and April 2015, to investigate if a 3-month diet rich in fruit, vegetables, whole grains, and omega-3 fatty acid-rich foods, named the fatigue reduction diet (FRD), improved fatigue and sleep compared to an attention control, named the general health curriculum (GHC). 30 stage 0 to III breast cancer survivors, who had completed cancer treatments, were randomized: 15 receiving the FRD and 15 the GHC. Primary outcome was change in fatigue, as measured by the brief fatigue Inventory, from baseline to 3 months analyzed using linear mixed models. Secondary analyses were changes in sleep quality, serum carotenoids, and fatty acids. RESULTS: From baseline to 3-month fatigue improved by 44 ± 39% in FRD compared to 8 ± 34% in GHC (p = 0.01); sleep quality improved by 2.5 ± 3.3 points in FRD, and diminished by 0.9 ± 2.3 in GHC (p = 0.03); serum total carotenoids (p < 0.01), ß-cryptoxanthin (p = 0.02), lutein (p = 0.05), zeaxanthin (p = 0.01), lycopene (p = 0.05), omega-3 fatty acids (p < 0.01), and ratio of omega-3:omega-6 fatty acids (p = 0.02) were significantly increased, and percent saturated fatty acids were decreased (p = 0.04) in FRD; γ-tocopherol was significantly increased in GHC (p = 0.03), and there was a significant visit by group difference for α-carotene between the study groups (p = 0.05). CONCLUSIONS: The FRD intervention improved fatigue and sleep in breast cancer survivors compared to the GHC. FRD diet could provide a non-toxic treatment strategy for persistent fatigue.

Preliminary differences in peripheral immune markers and brain metabolites between fatigued and non-fatigued breast cancer survivors: a pilot study.

Persistent cancer-related fatigue (PCRF) is one of the most troubling side-effects of breast cancer (BC) treatment. One explanatory model for PCRF is sickness behavior, which is a set of adaptive responses including sleepiness and depressed mood in reaction to an inflammatory trigger. Prior research has investigated differences in inflammatory cytokines between fatigued and non-fatigued BC survivors, but no study has examined differences in brain metabolites. Differences in inflammatory markers, and brain metabolites using proton magnetic resonance spectroscopy were evaluated within 16 fatigued and 13 non-fatigued BC survivors. Fatigued BC survivors had significantly higher ratios of two markers derived from brain metabolites; namely (a) creatine, normalized to total creatine (creatine + phosphocreatine (Cr/tCr)) ratio (P = 0.03) and (b) glutamate + glutamine (Glx) to N-acetyl-aspartate (NAA) ratio (P = 0.01) in the posterior insula compared to non-fatigued breast cancer survivor. Further, serum IL-6 was increased in fatigued women compared to non-fatigued women (P = 0.03), Using receiver operator curves (ROC) we determined that the posterior insula Glx/NAA ratio was the best predictor of fatigue with an overall area under the receiver operating characteristic curve (AUROC) of 79%, with a sensitivity of 81% and a specificity of 69%. However, posterior insula Glx/NAA, Cr/tCr and serum IL-6 were not significantly correlated with one another implying the possibility of independent biological mechanisms for PCRF rather than an interrelated mechanism as represented by the sickness behavior model. This study provides novel preliminary evidence of several distinct neurobiological changes in the posterior insula associated with PCRF in BC survivors. Future, longitudinal studies are needed to explore these distinct biological phenomena where changes through time in peripheral immune markers and brain metabolites are examined to determine if they correlate with changes in fatigue.

Acupressure for persistent cancer-related fatigue in breast cancer survivors (AcuCrft): a study protocol for a randomized controlled trial.

BACKGROUND: Despite high levels of clinically significant persistent cancer related fatigue in breast cancer survivors few treatments are currently available and most pose a significant burden on the part of the woman. Acupressure, a component of Traditional Chinese Medicine, has been shown to decrease fatigue levels by as much as 70% in cancer survivors while being inexpensive, non-toxic and an easy to use intervention. The primary aim of this study was to determine the efficacy of two types of self-administered acupressure (relaxation acupressure and stimulating acupressure), compared to standard of care on fatigue severity. Secondary aims were to evaluate the efficacy of two types of acupressure on sleep and kinetic parameters required for implementation of acupressure in a clinical setting; The purpose of this paper is to share the methodology used including challenges and insights. METHODS/DESIGN: This study is a three group, randomized clinical trial. 375 breast cancer survivors at least 12 months after completion of cancer treatments, with moderate to severe persistent fatigue, are being randomized to one of 3 groups: self-administered relaxation acupressure; self-administered stimulating acupressure; or standard of care. Participants are assessed at baseline, 3 weeks, and 6 weeks followed by a 4-week follow-up period. The primary aim is to examine the effect of 6-weeks of relaxation acupressure compared to stimulatory acupressure or standard of care on fatigue as assessed by: weekly self-report using the Brief Fatigue Inventory; objective daytime physical activity on actigraph; or fatigue patterns assessed 4-times daily using a visual analog scale. Secondary endpoints include depression, anxiety, self-efficacy, and sleep quality. DISCUSSION: This study has the potential to develop a low-cost, self-care intervention for the most troubling of late-term effects in breast cancer populations, fatigue. The methods used may lend constructive ideas to other investigators working with this population and/or intervention. TRIAL REGISTRATION: ClinicalTrial.Gov Trials Register NCT01281904.