Background In cancer patients with a poor prognosis, low skeletal muscle radiographic density is associated with higher mortality. Whether this association also holds for early-stage cancer is not very clear. We aimed to study the association between skeletal muscle density and overall mortality among early-stage (stage I–III) colorectal cancer (CRC) patients. Furthermore, we investigated the association between skeletal muscle density and both CRC-specific mortality and disease-free survival in a subset of the study population. Methods Skeletal muscle density was assessed in 1681 early-stage CRC patients, diagnosed between 2006 and 2015, using pre-operative computed tomography images. Adjusted Cox proportional hazard models were used to evaluate the association between muscle density and overall mortality, CRC-specific mortality and disease-free survival. Results The median follow-up time was 48 months (range 0–119 months). Low muscle density was detected in 39% of CRC patients. Low muscle density was significantly associated with higher mortality (low vs. normal: adjusted HR 1.91, 95% CI 1.53–2.38). After stratification for comorbidities, the association was highest in patients with ≥ 2 comorbidities (HR 2.11, 95% CI 1.55–2.87). Furthermore, low skeletal muscle density was significantly associated with poorer disease-free survival (HR 1.68, 95% CI 1.14–2.47), but not with CRC-specific mortality (HR 1.68, 95% CI 0.89–3.17) in a subset of the study population. Conclusion In early-stage CRC patients, low muscle density was significantly associated with higher overall mortality, and worse disease-free survival.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side-effect in colorectal cancer (CRC) patients. This study assessed the association between habitual dietary intake of magnesium or calcium and prevalence and severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For this prospective cohort study, 196 CRC patients were considered. Magnesium and calcium intake was determined using a food frequency questionnaire at diagnosis, during and after chemotherapy. Chronic CIPN was assessed 12 months after diagnosis using the quality of life questionnaire CIPN20. Prevalence ratios were calculated to assess the association between magnesium or calcium intake and the prevalence of CIPN. Multivariable linear regression analysis was used to assess the association between magnesium or calcium intake and severity of CIPN. CIPN was reported by 160 (82%) patients. Magnesium intake during chemotherapy was statistically significantly associated with lower prevalence of CIPN (prevalence ratio (PR) 0.53, 95% confidence interval (CI) 0.32, 0.92). Furthermore, higher dietary intake of magnesium during (β −1.08, 95% CI −1.95, −0.22) and after chemotherapy (β −0.93, 95% CI −1.81, −0.06) was associated with less severe CIPN. No associations were found for calcium intake and the prevalence and severity of CIPN. To conclude, we observed an association between higher dietary magnesium intake and lower prevalence and severity of CIPN in CRC patients.

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.

Purpose: Persistent fatigue among colorectal cancer (CRC) patients might be associated with unfavorable body composition, but data are sparse and inconsistent. We studied how skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at diagnosis are associated with fatigue up to 24 months post-diagnosis in stage I–III CRC patients.Methods: SMI, SMR, VAT, and SAT were assessed among 646 CRC patients using pre-treatment computed tomography images. Fatigue at diagnosis, at 6, and 24 months post-diagnosis was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The association of SMI, SMR, VAT, and SAT with fatigue (yes/no) was assessed using confounder-adjusted restricted cubic spline analyses.Results: Prevalence of fatigue at diagnosis was 18%, at 6 months 25%, and at 24 months 12%. At diagnosis, a significant (p = 0.01) non-linear association of higher levels of SAT with higher prevalence of fatigue was observed. Lower levels of SMR were linearly associated with higher prevalence of fatigue at 6 months post-diagnosis (overall associationp = 0.02). None of the body composition parameters were significantly associated with fatigue at 24 months.Conclusion: Having more SAT was associated with more fatigue at diagnosis, while low levels of SMR were associated with more fatigue at 6 months post-diagnosis.Implications for Cancer Survivors: Our results suggest that it may be interesting to investigate whether interventions that aim to increase SMR around the time of diagnosis may help to lower fatigue. However, more knowledge is needed to understand the mechanisms behind the association of SMR with fatigue.