A bio-behavioral model of systemic inflammation at breast cancer diagnosis and fatigue of clinical importance two years later.

BACKGROUND: We aimed to generate a model of cancer-related fatigue (CRF) of clinical importance two years after diagnosis of breast cancer building on clinical and behavioral factors and integrating pre-treatment markers of systemic inflammation. METHODS: Women with stage I-III HR+/HER2- breast cancer were included from the multimodal, prospective CANTO cohort (NCT01993498). The primary outcome was global CRF of clinical importance (EORTC QLQ-C30≥40/100) two years after diagnosis (year-2). Secondary outcomes included physical, emotional, and cognitive CRF (EORTC QLQ-FA12). All pre-treatment candidate variables were assessed at diagnosis, including inflammatory markers (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon gamma, IL-1 receptor antagonist, TNF-α, and C-reactive protein), and were tested in multivariable logistic regression models implementing multiple imputation and validation by 100-fold bootstrap resampling. RESULTS: Among 1208 patients, 415 (34.4%) reported global CRF of clinical importance at year-2. High pre-treatment levels of IL-6 (Quartile 4 vs.1) were associated with global CRF at year-2 (adjusted Odds Ratio [aOR]: 2.06 [95% Confidence Interval 1.40-3.03]; p=0.0002; AUC=0.74). Patients with high pre-treatment IL-6 had unhealthier behaviors, including being frequently either overweight or obese (62.4%; mean BMI 28.0 [SD 6.3] Kg/m2) and physically inactive (53.5% did not meet WHO recommendations). Clinical and behavioral associations with CRF at year-2 included pre-treatment CRF (aOR vs no: 3.99 [2.81-5.66]), younger age (per 1-year decrement: 1.02 [1.01-1.03]), current smoking (vs never: 1.81 [1.26-2.58]), and worse insomnia or pain (per 10-unit increment: 1.08 [1.04-1.13], and 1.12 [1.04-1.21], respectively). Secondary analyses indicated additional associations of IL-2 (aOR per log-unit increment:1.32 [CI 1.03-1.70]) and IL-10 (0.73 [0.57-0.93]) with global CRF and of C-reactive protein (1.42 [1.13-1.78]) with cognitive CRF at year-2. Emotional distress was consistently associated with physical, emotional, and cognitive CRF. CONCLUSIONS: This study proposes a bio-behavioral framework linking pre-treatment systemic inflammation with CRF of clinical importance two years later among a large prospective sample of survivors of breast cancer.

Land- and water-based aerobic exercise program on health-related outcomes in breast cancer survivors (WaterMama): study protocol for a randomized clinical trial.

BACKGROUND: Breast cancer is a prevalent form of cancer among women worldwide, often accompanied by physical and psychological side effects due to the disease and the treatment's aggressiveness. Regular physical exercise has emerged as a non-pharmacological approach to improve the quality of life of breast cancer survivors. We herein report the protocol of the WaterMama Study, which aims to evaluate the effects of land- or water-based aerobic exercise programs, compared to a health education program, on cancer-related fatigue and other health-related outcomes in breast cancer survivors. METHODS: The WaterMama trial is a randomized, single-blinded, three-arm, parallel, superiority trial. We aim to recruit 48 women ≥ 18 years of age who have completed primary treatment for stage I-III breast cancer. Participants are randomly allocated in a 1:1:1 ratio to 12-week interventions of aerobic exercise training programs either in the aquatic or land environment (two weekly 45-min sessions) plus health education (a weekly 45-min session), or an active-control group receiving health education alone (a weekly 45-min session). The primary outcome is cancer-related fatigue, and the secondary outcomes include cardiorespiratory fitness, muscular performance, muscle morphology, functional capacity, mental health, cognitive function, pain, and quality of life. Outcomes assessments are conducted before and after the 12-week intervention period. The analysis plan will employ an intention-to-treat approach and per protocol criteria. DISCUSSION: Our conceptual hypothesis is that both aerobic exercise programs will positively impact primary and secondary outcomes compared to the health education group alone. Additionally, due to its multi-component nature, we expect the aquatic exercise program promote more significant effects than the land exercise program on cancer-related fatigue, muscular outcomes, and pain. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov NCT05520515. Registered on August 26, 2022. https://clinicaltrials.gov/ct2/show/NCT05520515.

Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

PURPOSE: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). METHODS: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. RESULTS: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). CONCLUSION: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Effects of concurrent aerobic and strength training in women diagnosed with non-metastatic breast cancer: a systematic review and meta-analysis.

PURPOSE: To investigate the potential impact of concurrent aerobic and strength training (CT) on women diagnosed with breast cancer. METHODS: Articles published in English and indexed in the PubMed, Web of Science, SPORTDiscus, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus databases from their inception to 12 December 2023 were searched. Eligible studies were randomized controlled trials that involved CT and assessed cardiorespiratory fitness, cancer-related fatigue, and quality of life (QoL) using specialized tools. Subgroup analyses were conducted as per treatment status and characteristics. Risk of bias was evaluated with the Cochrane risk-of-bias tool (RoB 2.0). RESULTS: This study included 29 studies involving 2071 participants. CT was found to significantly improve patients' cardiorespiratory fitness (weighted mean difference = 4.24 mL/kg/min, 95% confidence interval (CI) = 1.93-6.55, P < 0.001), cancer-related fatigue (standardized mean difference (SMD) = - 0.74, 95% CI = - 1.05 to - 0.44, P < 0.001), and QoL (SMD = 0.76, 95% CI = 0.50-1.01, P < 0.001). The analysis of secondary outcomes found that CT could significantly improve patients' body composition, anxiety, pain, sleep disorders, and anorexia and enhance upper and lower limb muscle strength, but was ineffective on depression. CONCLUSION: For women with breast cancer, CT significantly enhances cardiorespiratory fitness, alleviates cancer-related fatigue, and improves QoL. The health benefits of CT are inferior in the postmenopausal cohort compared to the overall study population. IMPLICATIONS FOR CANCER SURVIVORS: CT is advisable for female breast cancer survivors due to its significant effectiveness in mitigating cancer-related fatigue, enhancing cardiorespiratory fitness, and improving the QoL.

Effects of Jianpi Huayu Decoction on Th1/Th2 Immune Balance in Mice With Liver Cancer-Related Fatigue via the IL- 27/STAT1 Signaling Pathway.

Objective: The Chinese medicine Jianpi-Huayu decoction (, JPHY) can alleviate cancer-related fatigue in patients with liver cancer. However, its mechanism remains unclear. In this study, we used BALB/c mice with liver cancer model to investigate whether JPHY alleviates cancer-related fatigue by regulating Th1/Th2 immune balance; and the possible association with the IL-27/STAT1 signaling pathway. Methods: We established a mouse model of liver cancer fatigue. Mice were gavaged with physiological saline, low, medium, or high concentrations of JPHY respectively; and intraperitoneal injection of fludarabine (STAT1 pathway inhibitor) with JPHY for 21 days. We recorded the general condition of the mice, and assessed fatigue using scoring criteria and Exhausted Swimming Test. We calculated the spleen and thymus indices, performed H&E staining and immunohistochemical analysis on liver tumor tissues to observe the tumor proliferation marker ki67. We quantified the secretion levels of IFN-γ and IL-2 produced by Th1 cells in serum and splenic lymphocytes, as well as the secretion of IL-4, IL-10 by Th2 cells, and IL-27 in the signaling pathway through ELISA analysis. We evaluated the expression levels of p-STAT1 and STAT1 in spleen tissues using Western blot analysis. Results: JPHY exhibits a therapeutic effect on hepatocellular carcinoma-induced splenomegaly in murine models by upregulating the pro-inflammatory cytokines IFN-γ and IL-2 and downregulating the anti-inflammatory cytokines IL-4 and IL-10. Moreover, JPHY suppresses ki67 expression, reduces tumor-related inflammation infiltration, and ameliorates cancer-associated fatigue. Additionally, the expression of phosphorylated protein p-STAT1 is down-regulated. Conclusion: JPHY may improve the Th1/Th2 immune balance through its anti-inflammatory effects and promotion of IL-27-induced STAT1 phosphorylation, thereby alleviating fatigue in mice with liver cancer.

Impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in adults with leukemia.

BACKGROUND: Patients not only experience symptoms caused by cancer but also suffer from the accompanying psychological pain. Therefore, these patients do not have high quality of life. According to the World Health Organization, the incidence of leukemia in China in 2020 was 5.1/100000, the mortality rate was 3.3/100000, and the prevalence rate was 16.7/100000. Therefore, it is important to examine the influence of comorbid subthreshold depressive symptoms on leukemia patients. AIM: To determine the impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in leukemia patients, thereby providing a basis for early diagnosis and treatment in clinical practice. METHODS: A questionnaire survey was conducted among leukemia patients admitted to a tertiary hospital in Xi'an, Shaanxi Province, China, from August 2022 to December 2023. Patients with a score > 16 on the Chinese Classification of Mental Disorders (CCMD-3) and a Hamilton Depression Rating Scale score of 8-17 were classified as the subthreshold depressive group (n = 95), while 100 leukemia patients admitted during the same period were classified as the control group. Data were collected using Epidata 3.1 software, and comparisons were made between the two groups regarding general clinical data, the Piper Fatigue Scale (PFS), the Pittsburgh Sleep Quality Index (PSQI), the Numeric Rating Scale for pain assessment, laboratory indicators, and the occurrence of complications. RESULTS: In this survey, 120 leukemia patients with depression were preliminarily screened, 95 patients with subthreshold depression were ultimately selected as the subthreshold depression group, and 100 leukemia patients admitted during the same period were enrolled as the normal group. Comparison of basic clinical data between the two groups revealed no significant differences in age, sex, body mass index, cognitive function, or comorbidity with other chronic diseases. However, there were statistically significant differences in the use of radiotherapy and regular exercise between the two groups (P < 0.05). Comparisons of scales and laboratory indicators revealed no significant differences in albumin or PSQI scores between the two groups, but there were statistically significant differences in pain scores, PSQI scores, PFS scores, hemoglobin levels, and C-reactive protein levels (P < 0.05). Spearman's correlation analysis indicated that cancer-related fatigue was correlated with age, hemoglobin levels, C-reactive protein levels, pain, and regular exercise among leukemia patients with subthreshold depression. Multivariate regression analysis revealed that advanced age, combined radiotherapy, pain, and low hemoglobin levels were risk factors for cancer-related fatigue in leukemia patients with comorbid subthreshold depression, while regular exercise was a protective factor against cancer-related fatigue. Follow-up comparisons revealed a significantly lower overall incidence of complications in the control group (4%) than in the depressive group (24.21%; P < 0.001). CONCLUSION: Leukemia patients with comorbid subthreshold depressive symptoms experience more severe cancer-related fatigue and a higher incidence of complications. These findings may be related to advanced age, combined radiotherapy, pain, and low hemoglobin levels, while regular exercise may effectively alleviate symptoms.

Identifying relevant factors influencing cancer-related fatigue in patients with diffuse large B-cell lymphoma during chemotherapy.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a rapidly growing malignant tumor, and chemotherapy is one of the treatments used to combat it. Although advancements of science and technology have resulted in more and more patients being able to receive effective treatment, they still face side effects such as fatigue and weakness. It is important to thoroughly investigate the factors that contribute to cancer-related fatigue (CRF) during chemotherapy. AIM: To explore the factors related to CRF, anxiety, depression, and mindfulness levels in patients with DLBCL during chemotherapy. METHODS: General information was collected from the electronic medical records of eligible patients. Sleep quality and mindfulness level scores in patients with DLBCL during chemotherapy were evaluated by the Pittsburgh Sleep Quality Index and Five Facet Mindfulness Questionnaire-Short Form. The Piper Fatigue Scale was used to evaluate the CRF status. The Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to evaluate anxiety and depression status. Univariate analysis and multivariate regression analysis were used to investigate the factors related to CRF. RESULTS: The overall average CRF level in 62 patients with DLBCL during chemotherapy was 5.74 ± 2.51. In 25 patients, the highest rate of mild fatigue was in the cognitive dimension (40.32%), and in 35 patients the highest moderate fatigue rate in the behavioral dimension (56.45%). In the emotional dimension, severe fatigue had the highest rate of occurrence, 34 cases or 29.03%. The CRF score was positively correlated with cancer experience (all P < 0.01) and negatively correlated with cancer treatment efficacy (all P < 0.01). Tumor staging, chemotherapy cycle, self-efficacy level, and anxiety and depression level were related to CRF in patients with DLBCL during chemotherapy. CONCLUSION: There was a significant correlation between CRF and perceptual control level in patients. Tumor staging, chemotherapy cycle, self-efficacy level, and anxiety and depression level influenced CRF in patients with DLBCL during chemotherapy.

Trajectory patterns and predictors of cancer-related fatigue in postoperative lung cancer patients receiving chemotherapy.

PURPOSE: Cancer-related fatigue (CRF) is a chronic symptom that can affect the overall functioning of lung cancer patients throughout the course of the disease. However, there is limited research on the trajectory and predictors of CRF specifically in lung cancer patients. Furthermore, few studies have investigated the predictive role of positive psychological and social factors in relation to CRF. This study aimed to explore the trajectory of CRF and its predictors in postoperative chemotherapy patients with lung cancer. METHODS: A total of 202 lung cancer patients who underwent surgery and received adjuvant chemotherapy were recruited for this study. Baseline questionnaires were completed, covering sociodemographic information, disease details, CRF levels, personality traits, psychological resilience, and social support. CRF was assessed at three time points: first chemotherapy (T1), 3 months after chemotherapy (T2), and 6 months after chemotherapy (T3). Latent class growth modeling (LCGM) was used to identify distinct developmental trajectories of CRF. Logistic regression analysis was employed to examine predictors of CRF within different patient groups. RESULTS: The LCGM analysis revealed three distinct CRF trajectories: persistent high fatigue group (30.7%), rising fatigue group (30.7%), and no fatigue group (38.6%). Cancer stage (OR = 7.563, 95% CI = 2.468-23.182, P < 0.001), melancholic personality (OR = 6.901, 95% CI = 1.261-37.764, P = 0.026), and high psychological resilience (OR = 0.171, 95% CI = 0.041-0.706, P = 0.015) were associated with the CRF trajectory. On the other hand, sanguine personality (OR = 0.254, 95% CI = 0.071-0.916, P = 0.036) and high social support (OR = 0.168, 95% CI = 0.045-0.627, P = 0.008) were associated with the increasing fatigue trajectory. CONCLUSIONS: This study demonstrated that 60% of lung cancer patients experienced persistent fatigue throughout the assessment period. Moreover, it confirmed the heterogeneity of CRF trajectories among lung cancer patients. The severity of CRF was found to be higher in patients with advanced clinical stages, depressive personality traits, and lower psychological resilience.

Identifying pre-habilitation targets for the mitigation of long-term side effects of chemotherapy in patients with early breast cancer.

BACKGROUND: Pre-treatment characteristics of women with early breast cancer that are associated with persistent fatigue or suboptimal health-related quality of life (HRQOL) post-chemotherapy need to be identified as potential targets for pre-habilitation. PATIENTS AND METHODS: Ancillary analysis of previously collected data from patients with newly diagnosed Stage I-III breast cancer scheduled to receive chemotherapy. The objective was to identify baseline (pre-chemotherapy) variables associated with meaningful deteriorations in fatigue and other measures of HRQOL from pre-treatment to 6 months after chemotherapy completion. Percentages are reported along with unadjusted and adjusted relative risks. RESULTS: In a sample of 249 women post-chemotherapy, 32% reported worsening fatigue (FACIT-F), 35% worsening Physical Well-Being (PWB), 16% worsening Functional Well-Being (FWB), 8% worsening Emotional Well-Being (EWB), and 30% worsening Social Well-Being (SWB). In multivariable (MV) analysis, variables that were significant in univariate analysis - Black race, high BMI, and baseline poorer EWB - remained significant for worsening post-chemotherapy fatigue (FACIT-F). In MV analysis that included race, education, falls, and baseline EWB, Black race and a positive falls history remained significant for worsening PWB. In MV analysis inclusive of race, Short Physical Performance Battery (SPPB) and FWB, lower SPPB and FWB remained significant predictors of worsening FWB. In MV analysis that included baseline Mental Health Index-Anxiety, EWB and SWB, a higher SWB and lower EWB remained significant for worsening SWB. CONCLUSION: Pre-chemotherapy characteristics in women with early-stage breast cancer that are associated with increased fatigue and reduced HRQOL post-treatment could be used to identify patients who may benefit from pre-habilitation interventions.

Fatigue in patients with metastatic breast cancer undergoing single-agent taxane-based chemotherapy: a real-world data global network.

Background: Cancer-related fatigue (CRF) occurs in nearly all patients with metastatic breast cancer (MBC). Objectives: This real-world analysis aimed to describe the prevalence and importance of fatigue in patients with MBC within 3 months of treatment with single-agent taxane-based chemotherapy during the timeframe of 2020-2022 in the United States and Europe. It was also conducted to assess whether there was a difference in relapsed patients compared to patients diagnosed de novo. Design: Electronic health records were analyzed from approximately 150 million patients to identify patients with MBC who underwent taxane treatment. Results: In 2021, 50,490 patients had MBC, of whom 16,170 were diagnosed de novo and 34,330 experienced relapse. The proportion of patients undergoing taxane-based chemotherapy was 7.5% (n = 1220) and 13.4% (n = 4590), respectively, and the prevalence of any fatigue and CRF was similar between the groups (24.6% versus 25.7% and 6.6% versus 5.4%, respectively). Conclusion: At least one in four patients with MBC undergoing taxane-based treatment will experience fatigue. This highlights the importance of validating screening tools to identify CRF, which is necessary to advance clinical trials aimed at investigating treatment strategies to improve patient-centered outcomes for fatigue.

Shenqi Fuzheng injection facilitates skeletal muscle mitophagy mediated by the ubiquitination of HIF-1α to ameliorate cancer-associated fatigue.

Cancer-related fatigue (CRF) significantly impacts the quality of life of cancer patients. This study investigates the therapeutic potential of Shenqi Fuzheng injection (SFI) in managing CRF, focusing on its mechanistic action in skeletal muscle. We utilized a CRF mouse model to examine the effects of SFI on physical endurance, monitoring activity levels, swimming times and rest periods. Proteomic analysis of the gastrocnemius muscle was performed using isobaric tags and liquid chromatography-tandem mass spectrometry to map the muscle proteome changes post-SFI treatment. Mitochondrial function in skeletal muscle was assessed via ATP bioluminescence assay. Furthermore, the regulatory role of the hypoxia inducible factor 1 subunit alpha (HIF-1α) signalling pathway in mediating SFI's effects was explored through western blotting. In CRF-induced C2C12 myoblasts, we evaluated cell viability (CCK-8 assay), apoptosis (flow cytometry) and mitophagy (electron microscopy). The study also employed pulldown, luciferase and chromatin immunoprecipitation assays to elucidate the molecular mechanisms underlying SFI's action, particularly focusing on the transcriptional regulation of PINK1 through HIF-1α binding at the PINK1 promoter region. Our findings reveal that SFI enhances physical mobility, reduces fatigue symptoms and exerts protective effects on skeletal muscles by mitigating mitochondrial damage and augmenting antioxidative responses. SFI promotes cell viability and induces mitophagy while decreasing apoptosis, primarily through the modulation of HIF-1α, PINK1 and p62 proteins. These results underscore SFI's efficacy in enhancing mitochondrial autophagy, thereby offering a promising approach for ameliorating CRF. The study not only provides insight into SFI's potential therapeutic mechanisms but also establishes a foundation for further exploration of SFI interventions in CRF management.

The definitions, assessment, and dimensions of cancer-related fatigue: A scoping review.

PURPOSE: Cancer-related fatigue (CRF) is challenging to diagnose and manage due to a lack of consensus on its definition and assessment. The objective of this scoping review is to summarize how CRF has been defined and assessed in adult patients with cancer worldwide. METHODS: Four databases (PubMed, Embase, CINAHL Plus, PsycNet) were searched to identify eligible original research articles published in English over a 10-year span (2010-2020); CRF was required to be a primary outcome and described as a dimensional construct. Each review phase was piloted: title and abstract screening, full-text screening, and data extraction. Then, two independent reviewers participated in each review phase, and discrepancies were resolved by a third party. RESULTS: 2923 articles were screened, and 150 were included. Only 68% of articles provided a definition for CRF, of which 90% described CRF as a multidimensional construct, and 41% were identical to the National Comprehensive Cancer Network definition. Studies were primarily conducted in the United States (19%) and the majority employed longitudinal (67%), quantitative (93%), and observational (57%) study designs with sample sizes ≥ 100 people (57%). Participant age and race were often not reported (31% and 82%, respectively). The most common cancer diagnosis and treatment were breast cancer (79%) and chemotherapy (80%; n = 86), respectively. CRF measures were predominantly multidimensional (97%, n = 139), with the Multidimensional Fatigue Inventory (MFI-20) (26%) as the most common CRF measure and "Physical" (76%) as the most common CRF dimension. CONCLUSION: This review confirms the need for a universally agreed-upon definition and standardized assessment battery for CRF.

Biological network comparison identifies a novel synergistic mechanism of Ginseng Radix-Astragali Radix herb pair in cancer-related fatigue.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng Radix and Astragali Radix are commonly combined to tonify Qi and alleviate fatigue. Previous studies have employed biological networks to investigate the mechanisms of herb pairs in treating different diseases. However, these studies have only elucidated a single network for each herb pair, without emphasizing the superiority of the herb combination over individual herbs. AIM OF THE STUDY: This study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF). METHODS: The compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies. RESULTS: In the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone. CONCLUSION: The herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.

Afraid and tired: A longitudinal study of the relationship between cancer-related fatigue and fear of cancer recurrence in long-term cancer survivors.

OBJECTIVE: Cancer-related fatigue (CRF) and fear of cancer recurrence (FCR) are two common concerns experienced by cancer survivors. However, the relationship between these two concerns is poorly understood, and whether CRF and FCR influence each other over time is unclear. METHODS: Data were from a national, prospective, longitudinal study, the American Cancer Society's Study of Cancer Survivors-I (SCS-I). Surveys were completed by 1395 survivors of 10 different cancer types at three time-points, including assessment 1.3 years (T1), 2.2 years (T2) and 8.8 years (T3) following their cancer diagnosis. CRF was assessed using the fatigue-inertia subscale of the Profile of Mood States, and FCR by the FCR subscale of the Cancer Problems in Living Scale. Multiple group random intercepts cross-lagged panel models investigated prospective associations between CRF and FCR. RESULTS: For younger participants (at or below median age of 55 years, n = 697), CRF at T1 and T2 marginally and significantly predicted FCR at T2 and T3, respectively, but no lagged effects of FCR on subsequent CRF were observed. Cross-lagged effects were not observed for survivors over 55 years of age. CONCLUSION: Both CRF and FCR are debilitating side effects of cancer and its treatments. Given that CRF may be predictive of FCR, it possible that early detection and intervention for CRF could contribute to lowering FCR severity.

Uncertainty affects cancer-related fatigue among breast cancer women undergoing peripherally inserted central catheter chemotherapy: the chain mediating role of psychological resilience and self-care.

BACKGROUND: Breast cancer patients undergoing chemotherapy via peripherally inserted central catheter often experience serious behavioral and psychological challenges, with uncertainty and cancer-related fatigue being prevalent issues that profoundly impact prognosis. Therefore, this study aimed to investigate the relationship between uncertainty and cancer-related fatigue by employing a chain mediation model to examine the potential mediating roles of psychological resilience and self-care. METHODS: A cross-sectional study was conducted with 223 breast cancer patients receiving peripherally inserted central catheter chemotherapy at two tertiary affiliated hospitals of China Medical University in Liaoning, China, from February 2021 to December 2022. Participants completed self-reported questionnaires to assess uncertainty, psychological resilience, self-care, and cancer-related fatigue. The collected data were subsequently analyzed using Pearson's correlation analysis, hierarchical regression analysis, and mediation analysis. RESULTS: Uncertainty exhibited a significant positive correlation with cancer-related fatigue (p < 0.01) and a negative correlation with psychological resilience (p < 0.01) and self-care (p < 0.01). Uncertainty was found to impact cancer-related fatigue through three pathways: psychological resilience mediated the relationship between uncertainty and cancer-related fatigue (mediating effect = 0.240, 95% confidence interval: 0.188 to 0.298, effect ratio = 53.22%); self-care also mediated this relationship (mediating effect = 0.080, 95% confidence interval: 0.044 to 0.121, effect ratio = 17.74%); furthermore, there was a significant joint mediating effect of psychological resilience and self-care on the association between uncertainty and cancer-related fatigue (mediating effect = 0.042, 95% confidence interval: 0.021 to 0.068, effect ratio o = 9.31%). CONCLUSION: The findings of this study revealed that uncertainty not only directly influenced cancer-related fatigue, but also operated through the mediating effect of psychological resilience, self-care, and sequential mediation of psychological resilience and self-care. Interventions tailored for breast cancer patients receiving peripherally inserted central catheter chemotherapy should target these factors to help alleviate uncertainty, enhance psychological resilience, and improve self-care practices, thereby ameliorating cancer-related fatigue.

Bibliometric and visualization analyses of cancer-related fatigue research published worldwide from 2001 to 2023.

Objective: Cancer seriously endangers human health and represents a global public health issue. Cancer-related fatigue (CRF) is a distressing and persistent sense of exhaustion caused by cancer or cancer treatment, widely prevalent among cancer patients. This study aims to summarize emerging trends and provide directions for future research of CRF through bibliometric and visualization analyses. Methods: A systematic search in the Web of Science Core Collection database from 2001-01-01 to 2023-05-18 were conducted. Only reviews and articles written in English were considered. CiteSpace and the R were used for bibliometric and visualization analyses. Results: The analysis revealed that 2,566 studies on CRF have been published by 1,041 institutions in 70 countries so far. The number of articles published and cited annually have been steadily increasing. Eduardo Bruera published the most articles, and Julienne E Bower is the most co-cited author. The University of Texas System is the leading institution in cancer-related fatigue research. The United States and China have the largest number of publications. Supportive Care in Cancer published the most articles, and Journal of Clinical Oncology is the most co-cited journal. "Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis", authored by Mustian KM et al. and published in JAMA Oncology was the most co-cited document. Keyword analysis indicated that research focus had shifted from "epoetin alpha" and "anemia" to "risk factors", "systematic review", "acupuncture", "anxiety", "traditional Chinese medicine" and "guidelines". Conclusion: In conclusion, this analysis provides comprehensive research trends and knowledge network maps of CRF. Clinical physicians should concurrently focus on the anemia, insomnia, anxiety, and depression status of patients when assessing or managing CRF. Improvements in related risk factors also contribute to alleviating fatigue. Furthermore, it is essential to pay attention to authoritative CRF guidelines. Acupuncture and traditional Chinese medicine also have therapeutic potential, which merits further investigation. Researchers should draw attention to the crucial roles of inflammation, hypoxia, and mitochondrial dysfunction, which could be the frontiers.

Infrared laser moxibustion for cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors.

AIM: We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients. METHODS: This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA). RESULTS: The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial η2 = 0.333). The Nuvastatic™ group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial η2 = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial η2 = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen's d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). CONCLUSION: Nuvastatic™ is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11-05-2020.

The effect of self-designed metabolic equivalent exercises on cancer-related fatigue in patients with gastric cancer: A randomized controlled trial.

AIMS: To investigate the effect of Self-designed Metabolic Equivalent Exercises (SMEE) on cancer-related fatigue in patients with gastric cancer. METHODS: 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ-C30 Quality of Life Scale were used to measure cancer-caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. RESULTS: After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow-up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ-C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p < 0.001) subscales; in the SMEE group, QLQ-C30 scores in somatic (2.00 ± 0.27 vs. 1.31 ± 0.26, p < 0.001), emotional (2.67 ± 0.58 vs. 2.07 ± 0.48, p < 0.001), and social (3.23 ± 0.58 vs. 1.64 ± 0.51, p < 0.001) functioning were significantly higher than those in the control group, with significant improvements in fatigue (p < 0.001), nausea/vomiting (p = 0.014), shortness of breath (p < 0.001), constipation (p < 0.001), and diarrhea (p = 0.001) dimensions. CONCLUSION: The self-programmed metabolic equivalent manipulation as an exercise intervention could effectively reduce the degree of cancer-caused fatigue and improve quality of life in patients with gastric cancer.

Cancer-related fatigue and activities of daily living: lessons learned from the COVID-19 pandemic.

BACKGROUND: Cancer-related fatigue is a prevalent condition in all stages of oncologic disease that is poorly diagnosed, with a negative impact on physical function to perform activities of daily living. Fatigue is also one of the main manifestations in post-COVID-19 syndrome, and few studies have explored the functionality of cancer patients after infection by the new coronavirus. This study was designed to assess cancer-related fatigue symptoms and their implications on physical function and quality of life during the pandemic. METHODOLOGY: An observational study with a cross-sectional survey in cancer patients ≥ 18 years of age was conducted. The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F), the perception of asthenia and performance status were evaluated, and the differences between groups according to the history of COVID-19 were calculated. RESULTS: A total of 60 cancer patients had an average age of 33.5 ± 10.11 years, 73.3% were female, and 98.3% had an Eastern Cooperative Oncology Group-Performance Status level < 2. Severe fatigue was found in 43.3% of patients, and the average FACIT-F score was 33.5 ± 10.11. The proportion of coronavirus infection was 13,3%, and the performance of this group was worse on the scale compared to the group without infection (25 ± 10,40 vs. 34,81 ± 9,50 [p = 0,009]). There was a significant correlation between visual analog scale values and FACIT-F scale scores (Pearson's r = -0.76). CONCLUSION: SARS-CoV-2 infection could increase cancer-related fatigue symptoms, limiting activities of daily living and impairing quality of life.