Background Fatigue is one of the most debilitating side effects of cancer therapy. Identifying biomarkers early during cancer therapy may help us understand the biologic underpinnings of the persistence of fatigue following therapy. Objective We aimed to identify early biomarkers of fatigue by examining correlations of levels of cytokines during external beam radiation therapy (EBRT) with persistence of fatigue one year following treatment completion in men with non-metastatic prostate cancer (NM-PC). Methods A sample of 34 men with NM-PC scheduled to receive EBRT were followed at baseline (T1), midpoint of EBRT (T2), and one year following EBRT (T3). Demographic and clinical data were obtained by chart review. The Functional Assessment of Cancer Therapy-Fatigue (FACT-F) was administered to measure fatigue levels. Plasma cytokine levels were determined at T1 and T2 using the Bio-Rad Bio-Plex Cytokine Assay Kits. Results Significant correlations were observed between levels of IL-3, IL-8, IL-9, IL-10, IL-16, IP10, IFNα2, IFNγ, and SDF1α at T2 with worsening of fatigue from T1 to T3. Conclusions Immunological changes prior to chronic fatigue development may reflect the long term response to radiation therapy-induced damage. Implications for Practice Early biomarkers for chronic fatigue related to cancer therapy will help advance our understanding of the etiology of this distressing symptom and will help nurses identify patients at risk for developing chronic fatigue after cancer treatment. This information will also aide in patient education, as well as symptom management.
Purpose Fatigue is the most ubiquitous side effect of cancer treatment, but its etiology remains elusive. Further investigations into cancer-related fatigue pathobiology necessitate the expanded use of animal models. This study describes the development of a murine model of radiation-induced fatigue. Methods Voluntary wheel running activity measured fatigue in 5–8 week-old, male C57BL/6 mice before and after γ irradiation totaling 2400 cGy (3 consecutive days × 800 cGy daily fractionated doses) to the lower abdominal areas. Three trials confirmed fatigue behavior at this dose. Anhedonia, body weight, and hemoglobin were also measured. Gastrointestinal, skeletal muscle, and bone marrow tissue samples were evaluated for signs of damage. Results In two validation trials, irradiated mice (trial 1, n=8; trial 2, n=8) covered less cumulative distance in kilometers post-irradiation (trial 1, mean=115.3±12.3; trial 2, mean=113.6±21.8) than sham controls (trial 1, n=5, mean=126.3±5.7, p=0.05; trial 2, n=8, mean=140.9±25.4, p=0.02). Decreased mean daily running distance and speed were observed during the last four hours of the dark cycle in irradiated mice compared to controls for two weeks post-irradiation. There were no differences in saccharin preference or hemoglobin levels between groups, no effect of changes in body weight or hemoglobin on wheel running distance, additionally, histology showed no damage to muscle, bone marrow, or gastrointestinal integrity, with the latter confirmed by ELISA. Conclusion We characterized a novel mouse model of fatigue caused by peripheral radiation and not associated with anemia, weight changes, or anhedonia. This model provides opportunities for detailed study of the mechanisms of radiation-induced fatigue.
Objective The study’s purpose was to develop symptoms cluster model that can describe factors of FMS associated with fatigue severity as reported by the sample. The study will also explore FMS clinical symptom sub-clusters based on varying symptom intensities. Methods FMS individuals (n = 120; 82% between 31–60 years of age, 90% women, 59% Caucasian) diagnosed with the 1990 or 2010 American College of Rheumatology diagnostic criteria were enrolled. Participants completed multiple validated self-report questionnaires to measure fatigue, pain, depression, anxiety, pain catastrophizing, daytime sleepiness, cognitive function, and FMS-related polysymptomatic distress. Cluster analysis using SPSS 19.0 and Structural Equation Modeling using AMOS 17.0 were used. Results Final Structural Equation Modeling symptoms cluster model showed good fit and revealed that FMS fatigue was associated with widespread pain, symptoms severity, pain intensity, pain interference, cognitive dysfunction, catastrophizing, anxiety, and depression (χ2 = 121.72, df = 98, p > 0.05, χ2/df = 1.242, CFI = 0.982, RMSEA = 0.045). Two distinct clinical symptom sub-clusters emerged; sub-cluster 1 (78% of total subjects) defined by widespread pain, unrefreshed waking, and somatic symptoms and sub-cluster 2 (22% of total subjects) defined by fatigue and cognitive dysfunction with pain being a less severe and less widespread complaint. Conclusion Overall, sub-cluster 1 had more intense symptoms than sub-cluster 2. FMS symptoms may be categorized into two clinical sub-clusters. These findings have implications for an illness whose diagnosis and management are symptom-dependent. A longitudinal study capturing the variability in symptom experience of FMS subjects is warranted.
Purpose: Cancer-related fatigue is a common complaint during cancer treatment and is often associated with cognitive impairment. This study examined cognitive deficits that were associated with fatigue symptoms during external-beam radiation therapy (EBRT) in men with localized prostate cancer. Methods: A total of 36 participants were enrolled and followed up at baseline, 24 h, 7 days, 14 days after EBRT initiation, at midpoint, and at completion of EBRT. Fatigue was measured by self-report using the Functional Assessment of Cancer Therapy – Fatigue (FACT-F), and cognitive impairment by the Computer Assessment of Mild Cognitive Impairment (CAMCI®). Results: Subjects with increased fatigue during EBRT reported a significant decline in cognitive function and had difficulties with CAMCI®’s route finding and item recall tasks during EBRT. Increased fatigue during EBRT was associated with perceived cognitive difficulties in executive function and recognition memory, but not with attention or verbal memory. Conclusions: Our results suggest that there might be specific cognitive domains that are associated with increased fatigue during EBRT. These findings will provide important information for targeting specific cognitive domains using pharmacotherapy or behavioral interventions. CAMCI® is a valuable tool for psycho social providers to detect subtle cognitive impairment in fatigued cancer patients in a clinical setting.
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