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.
CONCLUSIONS: 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.
BACKGROUND: The study was prospectively registered at ClinicalTrials.gov NCT05520515. Registered on August 26, 2022. https://clinicaltrials.gov/ct2/show/NCT05520515.

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.

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.

UNASSIGNED: Cancer-related fatigue (CRF) occurs in nearly all patients with metastatic breast cancer (MBC).
UNASSIGNED: 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.
UNASSIGNED: Electronic health records were analyzed from approximately 150 million patients to identify patients with MBC who underwent taxane treatment.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.
OBJECTIVE: 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.
CONCLUSIONS: 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.

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.
OBJECTIVE: 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).
CONCLUSIONS: 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.

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.
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.
CONCLUSIONS: 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.

OBJECTIVE: 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.

OBJECTIVE: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.

OBJECTIVE: 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).
CONCLUSIONS: 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.