The relationship between the latent profiles of cancer-related fatigue characteristics and exercise adherence in colorectal cancer patients

The influence of self- and autonomic regulation on cancer-related fatigue and distress in breast and colorectal cancer patients—A prospective study

This study aimed to improve cancer-related fatigue (CRF) and health outcomes of colorectal cancer patients by understanding the status quo of CRF, exploring the relations of coping, anxiety symptoms, depressive symptoms, body image perception and CRF, and also identifying the factors affecting CRF based on a generalized linear modeling approach. An exploratory cross-sectional study was conducted on 370 colorectal cancer patients at two hospitals in Anhui Province, China, from July 2020 to February 2021. The data were collected by using general information questionnaire, cancer fatigue scale, simplified coping style questionnaire, generalized anxiety disorder-7 scale, patient health questionnaire-9, and body image scale. Descriptive statistics, t-tests, one-way analysis of variance, Pearson correlation analyses, and generalized linear model analyses were applied to analyze the data. The average CRF score of the patients was 21.612 (SD=6.160), with a prevalence rate of 69.4% for clinically relevant fatigue. The generalized linear model revealed that: In step 1, gender (female) (B=1.799, Waldχ2=7.506, p=0.006), per capita monthly income (1001-3000 RMB) (B=-1.673, Waldχ2=5.536, p=0.019) and treatment modalities (chemotherapy+others) (B=2.425, Waldχ2=8.211, p=0.004) were related to CRF. In step 2, depressive symptoms (B=1.223, Waldχ2=129.019, p<0.001) and negative coping strategies (B=0.215, Waldχ2=11.347, p=0.001) exhibited significant positive correlations with CRF, positive coping strategies (B=-0.319, Waldχ2=59.175, p<0.001) showed significant negative correlations with CRF; While anxiety symptoms (B=0.162, Waldχ2=1.840, p=0.175) and body image perception (B=0.013, Waldχ2=0.048, p=0.826) had no correlations with CRF. The prevalence of CRF was relatively high among colorectal cancer patients. Coping and depressive symptoms were the modifiable influencing factors of CRF. Tailored interventions dedicated to promoting positive coping behavior, diminishing negative coping behavior and reducing depressive symptoms may improve the CRF of patients with colorectal cancer. Healthcare providers working with these patients should receive corresponding education and training in these complementary treatments. Additionally, when developing non-pharmacological interventions, appropriate consideration of the patients' gender, income condition and the type of anticancer treatment is also necessary.

Background: Cancer-related fatigue (CRF) affects up to 90% of patients with cancer during chemotherapy and persists in approximately 30% of patients after treatment completion, with some patients describing CRF as “devastating,” “never-ending,” and “totally consuming.” For patients with early-onset cancer (diagnosed&amp;lt;50 years) in particular, CRF is associated with worse quality of life and lower likelihood of returning to normal daily activities, including work. Alterations in certain metabolic pathways have been hypothesized to influence the development of CRF. The purpose of the present study is to identify differences in metabolic longitudinal predictors of CRF in a prospective cohort of patients with colorectal cancer (CRC) using serum metabolomics data. Methods: The ColoCare Study includes six U.S. sites and one Germany site and consists of men and women ages 18 to 89 at diagnosis with newly diagnosed primary CRC of stage I-IV. Patients are consented during a pre-surgery visit to complete questionnaires, provide biologic specimens at multiple time points, and for medical record reviews. Patients were categorized as early (age&amp;lt;50) or later-onset (age≥50). CRF was measured using the three-item fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) before CRC surgery (baseline), and 6, 12, and 24 months post-surgery. CRF scores were categorized as no, low, moderate, and high CRF using previously validated cutpoints. Using blood specimens at each time point, we performed semi-targeted metabolomics to identify aqueous metabolites following comprehensive protocols for measurement and quality control. Using multivariable ordinal logistic regression, we assessed the association between 1) individual metabolites and CRF cross-sectionally at each timepoint, and 2) metabolites measured at baseline and 6 months post-surgery and CRF at 12 months post-surgery. We adjusted for multiple testing using the number of effective independent tests. Further analyses using machine learning methods and metabolic pathway analysis are ongoing. Results: ColoCare Study participants with at least one measurement of CRF and metabolomic profiling (N=1,098) were included in the present study. Early-onset and later-onset patients had similar CRF prevalence. N=173 distinct polar metabolites were detected. Five metabolites (e.g. tryptophan metabolites, xenobiotic metabolites) were inversely associated and a nicotine metabolite (C16H20N2O8) was positively associated with CRF at baseline only among later-onset patients. A phenylalkylamine xenobiotic metabolite (C18H31NO) measured at 6 months post-surgery was inversely associated with CRF at 12 months post-surgery only among early-onset patients. Conclusions: CRF is prevalent in both early-onset and late-onset CRC patients. Metabolites associated with CRF in patients with CRC differed by age at onset. Further research profiling metabolic pathways associated with CRF by age can aid in identifying targetable mechanisms of CRF in early-onset CRC patients. Citation Format: Nicole C. Loroña, Mary Playdon, James Cox, Xiaoyin Li, Aasha I. Hoogland, Patricia A. Erickson, Maria F. Gomez, Sheetal Hardikar, Mmadili N. Ilozumba, Jennifer Ose, Anita Peoples, Brent Small, Victoria Damerell, Vaia Florou, Mark Lewis, Shannon M. Christy, William Grady, Biljana Gigic, David Shibata, Doratha A. Byrd, Adetunji Toriola, Christopher I. Li, Cornelia Ulrich, Heather S L. Jim, Jane C. Figueiredo. Differences in metabolomic profiles predictive of fatigue in early-onset vs. later-onset colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B038.

Objective To investigate the relationship between cancer-related fatigue (CRF) and quality of life (QOL) of the colorectal cancer patients.Methods In this study,patients diagnosed definitely as colorectal cancer were enrolled from November 2010 to January 2011 in this hospital.Piper Fatigue Scale was used to assess the CRF and QLQ-C30 was used to assess the QOL.Results 74 patients were enrolled in this study,and among them 28 patients had CRF(37.84％).Patients with CRF was significantly worse in QOL than patients without CRF.Physical function,role function,emotional function,social function and the general health subscale had a negative correlation with CRF,while pain,fatigue and loss of appetite had a positive correlation with it.Conclusions CRF had an impact on QOL,and this study will provide some reference information when the nurses take measures to intervene CRF and improve QOL of the colorectal cancer patients. Key words: Colorectal cancer; Cancer-related fatigue; Quality of life

This cross-sectional study aimed to describe cancer-related fatigue (CRF) in colorectal cancer (CRC) patients who were surgically treated with curative intent, identify subgroups at risk of elevated fatigue levels and explore associations between CRF and treatment burden. CRF is a prominent symptom among cancer patients. In patients treated for CRC, CRF is associated with adjuvant treatments, low quality of life and reduced ability to self-manage. One hundred thirty-four patients with CRC treated at a Norwegian university hospital between 2016-2018 were included. The Schwartz Cancer Fatigue Scale-6 and the Patient Experience with Treatment and Self-management questionnaires were applied for data collection. Statistical analyses included descriptive statistics and non-parametric approaches to analyse correlations and identify differences between groups. The study adhered to STROBE Statement checklist for reporting of cross-sectional studies. Median fatigue level was 10.0 (range: 7.0-13.0). Physical fatigue was higher than perceptual fatigue, with medians of 6.0 (interquartile range [IQR]: 3.0-13.0) and 4.0 (IQR: 3.0-12.0), respectively. Higher fatigue levels were associated with age <60years, advanced cancer and adjuvant treatments. Increased CRF was significantly associated with higher treatment burden on seven of the nine dimensions, adjusted for demographic and clinical variables. The association of fatigue and treatment burden was stronger in survivors <60years, with advanced cancer, 6-12months since surgery or who had more comorbid conditions. This study showed patients at risk of experiencing CRF following CRC treatment. It established proof of associations between CRF and treatment burden and identified subgroups of CRC patients where this association was stronger. Screening of CRF in CRC patients can help clinicians provide individualized treatment and care to manage CRF. Clinicians should consider the association between CRF and treatment burden, especially in subgroups of CRF patients.

Background: Cancer-related fatigue (CRF) is a prevalent and debilitating symptom among colorectal cancer (CRC) patients. This study aimed to identify genetic variants associated with CRF trajectories and assess their relationships with clinical and demographic factors. Methods: Participants (N=1,219) were recruited from the ColoCare Study across six U.S. sites and the University of Heidelberg in Germany. Eligible participants were adults (≥18 years) with a new diagnosis of primary colon or rectal cancer. CRF was assessed at five timepoints (baseline, 3, 6, 12, and 24 months) using the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) fatigue subscale. Longitudinal analysis of CRF patterns was performed using piecewise growth mixture models (GMMs), which identified three distinct trajectories: high, moderate, and low fatigue. Fatigue outcomes were assessed in three ways: as a binary variable (high vs. moderate/low trajectories), as a continuous measure (mean fatigue scores), and through an extreme phenotype approach (highest fatigue observed across all timepoints). Genome-wide association analyses (GWAS) were conducted using PLINK. Analyses were adjusted for potential confounders, including age, sex, cancer stage, smoking status, and population stratification (top two principal components). We performed fine-mapping analyses to identify independent secondary signals in known loci, focusing on SNPs previously associated with CRF and regions with p-values &amp;lt;5 × 10-6 in at least two of our GWAS models. Results: Among 1,219 CRC patients, 378 (31.0%) reported high fatigue, while 651 (53.4%) were categorized as having low/moderate fatigue. Significant differences in cancer-related fatigue were observed by race/ethnicity, smoking status, cancer stage, recurrence status, and receipt of neoadjuvant treatment. When examining fatigue as a binary outcome, a locus on chromosome 4 near LINC02505 was associated with higher risk of fatigue (rs6531463, OR = 3.25, 95% CI: 2.83-3.67, p=3.88 × 10-8). Several variants near NEK10 and SLC4A7 on chromosome 3 also showed suggestive associations (p-value range: 5×10−8&amp;lt;p&amp;lt;5×10−6). Similar results were observed when examining average fatigue as the outcome. The most significant locus was on chromosome 3p24.1 near NEK10 and SLC4A7 (rs7617094, OR = 0.57, 95% CI: 0.47-0.69, p=2.21 × 10-8). For extreme fatigue, loci on chromosomes 3p24.1 and 5q13.1 also were associated with elevated risk (p-value range: 5×10−8&amp;lt;p&amp;lt;5×10−6). Fine-mapping analyses identified 3 credible sets across 3 loci including 5q13.1, 3p24.1 and 5q13.1. Conclusion: This study investigates the genetic basis of CRF in CRC patients, identifying novel loci and refining known susceptibility regions. Key loci associated with CRF include LINC02505, NEK10, and SLC4A7. These findings if validated offer potential targets for interventions focused on CRF prevention and management.&amp;lt;/p&amp;lt;5×10&amp;lt;/p&amp;lt;5×10 Citation Format: Elham Kazemian, Qianxing Mo, Xiaoyin Li, Aasha I. Hoogland, Sylvia L. Crowder, Brian D. Gonzalez, Laura B. Oswald, Alix G. Sleight, Nathalie Nguyen, Nicole C. Lorona, Victoria Damerell, Khaled R. Komrokji, Kathi Mooney, Mary C. Playdon, Cornelia M. Ulrich, Christopher I. Li, David Shibata, Adetunji T. Toriola, Jennifer Ose, Anita R. Peoples, Erin M. Siegel, Julienne E. Bower, Biljana Gigic, Heather S. L. Jim, Jane C. Figueiredo. Exploring the genetic underpinnings of cancer-related fatigue in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2275.

e20608 Background: Fatigue severely reduces quality of life in many cancer patients. Cancer related fatigue (CRF) occurs with anaemia, during and after chemo- or radiotherapy and in advanced tumour states. The Cancer Fatigue Scale (CFS) is a well validated 15-item, 3-dimensional inventory (physical, cognitive, affective). Our classification procedure of its German version aimed at best separation of fatigue in cancer patients from healthy controls. Methods: CFS-D study data was combined from two studies that included CSF-D evaluations: a) 21 breast cancer (BC) and 7 colorectal cancer (CRC) patients (from a group of 57 cancer patients) and all 57 matched-pairs healthy controls (C); b) 41 BC and 25 CRC patients with chemotherapy. Analysing repeated ratings, four groups were found to significantly differ in global CFS-D (N female/male): C 65/27, CRC with (+) viscum album (VA) 27/34, BC + VA 110/0, BC without (-) VA 30/0. In cut-off analyses of sum- and subscales we iteratively categorized the data using moving thresholds and calculated their chi-square (X2) statistics when crossed with the study groups. CFS-D values were chosen as cut-off thresholds that yielded maximum X2 values when tested in 2x2-, 3x4-, and 4x4-tables. We plotted ROC curves to check for congruency of cut-off and ROC values. Results: Global CFS-D median (min.-max.) were: C 18 (2–38), CRC 22 (1–46), BC + VA 27 (0–54), and BC - VA 29.5 (7–48). For global CFS-D, cut-off and ROC analyses indicated ‘unclear’ CRF starting at 23 and ‘probable’ at 30. Subscale results were less definite; maybe with categories ‘unclear’/‘probable’ for dimensions ‘physical’: 9/15, ‘cognitive’: 9/11, ‘affective’: 6/8. Conclusions: The CFS-D is a highly reliable and valid global CRF questionnaire indicating categories ‘probable’ &gt;= 30, ‘unclear’ at 23–29 and ‘none’ &lt; 23. Thresholds for CFS-D subscales are less clear-cut and can not simply be calculated as proportional fractions of the total scale. No significant financial relationships to disclose.

Objective To explore the effect of mindfulness-based stress reduction (MBSR) on cancer-related fatigue and mental status of patients with non-small-cell lung cancer (NSCLC) who receive chemotherapy. Methods By convenience sampling, 67 patients with NSCLC receiving chemotherapy in the First People's Hospital of Lianyungang in Jiangsu Province were selected from June 2017 to December 2018 in this study. According to their admission time, they were divided into the observation group (n=34) and control group (n=33) . Conventional nursing care was given for the control group, apart from that, the MBSR exercise was adopted for the observation group, once a week and 8 times in total. Cancer Fatigue Scale (CFS) , Self-rating Anxiety Scale (SAS) , and Self-Rating Depression Scale (SDS) were used to compare the scores of their cancer fatigue, anxiety and depression between the two groups. Results Finally, 31 patients in the observation group and 32 patients in the control group completed the study. Before intervention, there was no statistical difference in CFS and each dimensional score in CFS, SAS and SDS scores between the two groups (P>0.05) ; after 8 weeks' intervention of MBSR, the CFS score and each dimensional score in CFS, SAS and SDS scores of the observation group were lower than those of the control group, and the differences were statistically significant (P<0.05) . Conclusions MBSR can effectively improve the NSCLC patients' cancer-related fatigue and reduce the level of anxiety and depression. Key words: Neoplasms, non-small-cell lung; Cancer-related fatigue; Mindfulness-based stress reduction; Anxiety; Depression

Specific Detection of Cytokeratin 20-Positive Cells in Blood of Colorectal and Breast Cancer Patients by a High Sensitivity Real-Time Reverse Transcriptase-Polymerase Chain Reaction Method

Background: Cancer-related fatigue represents one major cause of reduced quality of life in cancer patients and can seriously affect the physical, emotional, and cognitive functioning impeding coping with the disease. Options for effective treatment of cancer-related fatigue are limited, consisting only of non-pharmacologic interventions like physical activity, psychosocial, and mind-body interventions. Recent evidence suggests that vitamin D3 supplementation might alleviate cancer-related fatigue. However, confirmation in a randomized controlled trial is needed. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 456 colorectal cancer (CRC) patients aged 18 years and older are being recruited in three German rehabilitation clinics. Study inclusion requires hospitalization of at least 3 weeks at such a clinic, a diagnosis of non-metastatic CRC (stage I-III), surgical removal of the tumor within the past 9 months, and season-adapted vitamin D insufficiency or deficiency. Eligible patients are randomly assigned to a personalized regimen of vitamin D3 or placebo for 12 weeks. In the intervention group, a loading dose of 20,000 or 40,000 IU vitamin D3 will be administered daily during the first 11 days, followed by a maintenance dose of 2000 IU daily. Patients will complete questionnaires for secondary outcomes (fatigue subdomains, quality of life and subdomains, depression, functional well-being, and infection frequency). Blood and urine samples will be collected for analyses of safety parameters (hypervitaminosis D, hypercalcemia, hypercalciuria, and renal impairment) and efficacy biomarkers (25-hydroxyvitamin D, HbA1c, white blood cell count, leukocyte subtype counts, serum C-reactive protein, uric acid, creatinine, triglycerides, total, low- and high-density lipoprotein cholesterol). Discussion: This trial tests whether a personalized vitamin D3 dosing regimen reduces or prevents fatigue among non-metastatic CRC patients by treating the underlying vitamin D deficiency/insufficiency. If efficacy can be confirmed, personalized vitamin D3 supplementation could be used as a tertiary prevention measure in addition to non-pharmacological treatments of cancer-related fatigue in CRC patients. We expect to detect an effect of vitamin D3 supplementation on secondary outcomes like quality of life, depression, functional well-being, infections, inflammatory biomarkers, diabetes mellitus, and dyslipidemia. Trial registration: European Clinical Trials Database: EudraCT-No: 2019–000502–30, January 21, 2019; German Clinical Trials Register (DRKS): DRKS00019907, April 30, 2019.

Background: Cancer-related fatigue (CRF) is a common and burdensome symptom in cancer patients that is influenced by multiple factors. Identifying factors associated with CRF may help in developing tailored interventions for fatigue management. This study aimed to examine the correlates of CRF among colorectal cancer patients undergoing postoperative adjuvant therapy based on the theory of unpleasant symptoms. Methods: A cross-sectional study was implemented, and finally, a sample of 363 participants from one tertiary general hospital and one tertiary cancer hospital was purposively recruited. Data were collected using the general information questionnaire, cancer fatigue scale, the distress disclosure index, Herth hope index, and perceived social support scale. Univariate analysis and multiple linear regression analysis were performed to determine the correlates of CRF. Results: The mean score of CRF among colorectal cancer patients was 21.61 (SD = 6.16, 95% CI 20.98–22.25), and the fatigue degree rating was “moderate”. The multiple linear regression model revealed that 49.1% of the variance in CRF was explained by hope, sleep disorder, internal family support, self-disclosure, pain, and time since operation. Conclusions: Our study identified several significant, modifiable factors (self-disclosure, hope, internal family support, pain, and sleep disorder) associated with CRF. Understanding these correlates and developing targeted psychosocial interventions may be associated with the improvement of CRF in patients with colorectal cancer.

BACKGROUNDCancer-related fatigue (CRF) is the most common concomitant symptom in the treatment of colorectal cancer (CRC). Such patients often present with subjective fatigue state accompanied by cognitive dysfunction, which seriously affects the quality of life of patients.AIMTo explore the effects of cognitive behavior therapy (CBT) combined with Baduanjin exercise on CRF, cognitive impairment, and quality of life in patients with CRC after chemotherapy, and to provide a theoretical basis and practical reference for rehabilitation of CRC after chemotherapy. METHODSFifty-five patients with CRC after radical resection and chemotherapy were randomly divided into either an experimental or a control group. The experimental group received the intervention of CBT combined with exercise intervention for 6 mo, and indicators were observed and measured at baseline, 3 mo, and 6 mo to evaluate the intervention effect.RESULTSCompared with the baseline values, in the experimental group 3 mo after intervention, cognitive function, quality of life score, and P300 amplitude and latency changes were significantly better (P < 0.01). Compared with the control group, at 3 mo, the experimental group had significant differences in CRF, P300 amplitude, and quality of life score (P < 0.05), as well as significant differences in P300 latency and cognitive function (P < 0.01). Compared with the control group, at 6 mo, CRF, P300 amplitude, P300 latency, cognitive function and quality of life score were further improved in the experimental group, with significant differences (P < 0.01). The total score of CRF and the scores of each dimension were negatively correlated with quality of life (P < 0.05), while the total score of cognitive impairment and the scores of each dimension were positively correlated with quality of life (P < 0.05). CONCLUSIONCBT combined with body-building Baduanjin exercise can improve CRF and cognitive impairment in CRC patients after chemotherapy, and improve their quality of life.

Measurement of cancer-related fatigue and nutrition in the same colorectal cancer patient group using fast-track surgery has never been examined previously. The association between fatigue and nutritional status in the same patient group is thus worthwhile to be investigated. The aim of this study was to evaluate the relationship between fatigue and nutrition risk factors in colorectal cancer patients with fast-track surgery. This is a single-arm, observational study. Seventy eligible postoperative patients with colorectal cancer fast-track surgery were enrolled in this study. Patients completed the Cancer Fatigue Scale and the Patient-Generated Subjective Global Assessment (PG-SGA) besides routine perioperative laboratory examination. In this study, all patients were found to have cancer-related fatigue; 20% of the patients had severe fatigue. Furthermore, 94.29% of the patients were malnourished according to the PG-SGA score; the average was 15.585.18. Fatigue severity was significantly, positively correlated with nutrition status. White blood cells and serum calcium were significantly, positively related to both Cancer Fatigue Scale and PG-SGA scores. Fatigue and malnutrition commonly exist in patients with colorectal cancer experiencing fast-track surgery. Fatigue may reflect the nutritional status in this group of patients. Clinical nursing staff need to evaluate patients' fatigue status and nutritional status to provide the suitable clinical intervention when needed.

9021 Background: A subset of cancer patients has cognitive impairment and fatigue after chemotherapy (CTh). We evaluated these symptoms and potential mechanisms in CRC patients and healthy controls (HC). Methods: Cognitive function was evaluated in CRC patients and HC at baseline (pre-CTh), 6 and 12 months. Group 1A (Stage II/III) received CTh and Gr 1B (Stage I/II) no CTh. Gr 2 had limited metastatic CRC. All subjects completed cognitive assessment and questionnaires for fatigue, QOL, anxiety/depression, and perceived cognitive function. Blood tests evaluated: 10 cytokines, clotting factors, sex hormones, CEA, CBC and apolipoprotein genotyping as potential causal factors. Primary endpoints: cognitive function and fatigue (Gr. 1A &amp; 1B) at 12 months. Associations between results and demographic and disease-related factors were sought. Results: 359 CRC patients (173 Gr 1A, 116 Gr 1B, 70 Gr. 2) and 72 HC were assessed. Median age 58 (23-75 years); 58% male. Cognitive impairment: baseline Gr 1A 34% vs 1B 32.5% (p=.9), Gr 1 33% vs HC 10% (p&lt;0.001); 12 months Gr 1A 21% vs 1B 16% (p=0.43), Gr 1 19% vs HC 2% (p=0.001). Cognitive domains most affected: verbal &amp; visual memory, processing speed. Men had greater impairment than women (p&lt;0.009). Cognitive decline from 0-12 months: Gr 1A 30%, Gr 1B 19%, Gr 2 24%, and HC 16%. Perceived cognitive impairment at 12 months: Gr 1A 19% vs 1B 7% (p=.04), Gr 1 14% vs HC 0% (p=.009). Fatigue was greatest in Gr 1A (70%) at 6 months; at 12 months Gr. 1A 46% vs 1B 31% (p=0.056), Gr 2 60%, HC 36%. Cytokines were elevated in CRC patients compared to HC. No association was found with cognitive function and: fatigue, QOL, anxiety/depression, cytokines, sex hormones, clotting factors, CEA or apoE genotype. Objective cognitive function was associated with perceived cognitive function at baseline only. Fatigue at baseline was associated with hemoglobin and at 12 months with neutrophil count. Conclusions: Compared to HC, CRC patients had more cognitive impairment at baseline, 6 and 12 months; but impairment was not significantly different between those who did and did not receive CTh. The mechanisms of cognitive impairment remain unknown. Fatigue improved with time.

Simple SummaryFatigue is common among colorectal cancer patients. A healthier lifestyle may beneficially affect fatigue, although data are sparse. A healthier lifestyle may result in lower levels of inflammation, which is one of the suggested mechanisms by which lifestyle could influence fatigue. In an observational study, we investigated 1) whether a healthier lifestyle was associated with less fatigue among colorectal cancer patients, and 2) whether this association could be explained by inflammation. We showed that a healthier lifestyle was associated with less fatigue, and that inflammation levels mediated this association. Future intervention studies should investigate whether improving lifestyle after cancer diagnosis results in lowering of inflammation markers and subsequent fatigue.Fatigue is very common among colorectal cancer (CRC) patients. We examined the association between adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and fatigue among stage I-III CRC patients, and whether inflammation mediated this association. Data from two prospective cohort studies were used. Adherence to the WCRF/AICR recommendations was expressed as a score ranging from 0–7, and assessed shortly after diagnosis. Six months post-diagnosis, fatigue was assessed with the European Organization for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30), and in a subpopulation, the plasma levels of inflammation markers (IL6, IL8, TNFα, and hsCRP) were assessed. Multiple linear regression analyses were performed to investigate the association between adherence to the WCRF/AICR recommendations and fatigue. To test mediation by inflammation, the PROCESS analytic tool developed by Hayes was used. A higher WCRF/AICR adherence score was associated with less fatigue six months after diagnosis (n = 1417, β −2.22, 95%CI −3.65; −0.78). In the population of analysis for the mediation analyses (n = 551), the total association between lifestyle and fatigue was (β −2.17, 95% CI −4.60; 0.25). A statistically significant indirect association via inflammation was observed (β −0.97, 95% CI −1.92; −0.21), explaining 45% of the total association between lifestyle and fatigue (−0.97/−2.17 × 100). Thus, inflammation is probably one of the underlying mechanisms linking lifestyle to fatigue.