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Aim: The aim of this study was to longitudinally investigate dietary and lifestyle inflammation scores and their interaction in relation to risk of colorectal cancer (CRC) recurrence and all-cause mortality. Methods: Data of two prospective cohort studies among CRC survivors was used. Information about diet and/or lifestyle was available for 2739 individuals for at least one of the following time points: at diagnosis, six months after diagnosis and two years after diagnosis. The dietary and lifestyle inflammation scores (DIS and LIS) were used to evaluate the inflammatory potential of diet and lifestyle. Joint modelling, combining mixed models and Cox proportional hazards regression, were used to assess associations between DIS and LIS over time and CRC recurrence and all-cause mortality. Interactions between DIS and LIS were assessed using time-dependent Cox proportional hazard regression. Results: The median follow-up time was 4.8 (IQR 2.9–6.9) years for recurrence and 5.7 (IQR 3.5–8.5) years for all-cause mortality, with 363 and 453 events, respectively. A higher DIS as well as LIS was associated with a higher risk of all-cause mortality (HRDIScontinuous 1.09 95%CI 1.02; 1.15; HRLIScontinuous 1.24 95%CI 1.05; 1.46). Individuals who were in the upper tertile of both DIS and LIS had the highest all-cause mortality risk (HR 1.62 95%CI 1.16; 2.28), compared to the individuals in the lowest tertile of both DIS and LIS. No consistent associations with recurrence were observed. Conclusion: A more pro-inflammatory diet and lifestyle was associated with a higher risk of all-cause mortality, but not recurrence, in CRC survivors.

Introduction: Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be considered and in some patients surgery with curative intent may become feasible. The aim of this study was to evaluate the outcomes of patients treated with induction chemotherapy and to identify patient and/or tumor characteristics associated with survival. Material and methods: Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005 and 2021 were identified from an institutional database of a tertiary referral center. Response to therapy was assessed by (18F-FDG PET)/CT. Response to therapy and treatment options, including surgery or palliation, were discussed in the multidisciplinary tumor board. Overall survival (OS) was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. Results: 238 patients were identified. The majority had esophageal adenocarcinoma (68.9 %) and were treated with a taxane/platinum-based chemotherapy (79.4 %). Response evaluation was performed in 233 patients and 154 of 238 patients (64.7 %) underwent surgical exploration. Resection was performed in 127 patients (53.4 %) resulting in a median and 5-year OS of 26.3 months (95 % CI 18.8–33.8) and 29.6 %, respectively. Presence of T4b (HR = 2.01, 95 % CI 1.02–3.92) and poorly differentiated tumor (HR = 1.45, 95 % CI 1.02–2.10) was associated with worse survival (p = 0.04). Conclusion: In carefully selected patients with advanced disease not amenable for standard curative treatment, induction chemotherapy followed by esophagectomy may result in a 5-year overall survival of approximately 30 %.

Background: Capecitabine is an oral chemotherapeutic drug showing antitumor activity through inhibition of thymidylate synthase, an enzyme involved in folate metabolism. There are concerns about the high intake of certain vitamins, and specifically folate, during chemotherapy with capecitabine. Whether folate or folic acid, the synthetic variant of the vitamin, impact treatment toxicity remains unclear. Objective: We studied associations between intake and biomarkers of folate as well as folic acid and toxicities in patients with colorectal cancer (CRC) receiving capecitabine. Methods: Within the prospective COLON (Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that influence recurrence, survival, and quality of life) cohort, 290 patients with stage II to III CRC receiving capecitabine were identified. Dietary and supplemental intake of folate and folic acid were assessed at diagnosis and during chemotherapy using questionnaires (available for 280 patients). Plasma folate and folic acid levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) and were available for 212 patients. Toxicities were defined as toxicity-related modifications of treatment, including dose reductions, regimen switches, and early discontinuation. Associations of intake and biomarkers of folate and folic acid with toxicities were determined using Cox proportional hazards regression adjusted for age and sex. Results: In total, 153 (53%) patients experienced toxicities leading to modification of capecitabine treatment. Folate intake and plasma folate levels were not associated with risk of toxicities. However, use of folic acid-containing supplements during treatment (hazard ratio (HR) 1.81 and 95% confidence interval (CI) 1.15-2.85) and presence of folic acid in plasma at diagnosis (HR 2.09, 95% CI: 1.24, 3.52) and during treatment (HR 2.31, 95% CI: 1.29, 4.13) were associated with an increased risk of toxicities. Conclusions

Coffee consumption has been associated with a reduced risk of developing colorectal cancer (CRC). However, it is not clear whether coffee consumption is related to CRC progression. Hence, we assessed the association of coffee consumption with CRC recurrence and all-cause mortality using data from a prospective cohort study of 1719 stage I–III CRC patients in the Netherlands. Coffee consumption and other lifestyle characteristics were self-reported using questionnaires at the time of diagnosis. We retrieved recurrence and all-cause mortality data from the Netherlands Cancer Registry and the Personal Records Database, respectively. Cox proportional hazard regression models with and without restricted cubic splines were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, education, smoking status, cancer stage and tumor location. We observed 257 recurrences during a 6.2-year median follow-up and 309 deaths during a 6.6-year median follow-up. Consuming more than 4 cups/d of coffee compared to an intake of <2 cups/d was associated with a 32% lower risk of CRC recurrence (95% CI: 0.49, 0.94,). The association between coffee consumption and all-cause mortality was U-shaped; coffee intake seemed optimal at 3–5 cups/d with the lowest risk at 4 cups/d (HR: 0.68, 95% CI: 0.53, 0.88). Our results suggest that coffee consumption may be associated with a lower risk of CRC recurrence and all-cause mortality. The association between coffee consumption and all-cause mortality appeared nonlinear. More studies are needed to understand the mechanism by which coffee consumption might improve CRC prognosis.

Introduction: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until five years post-diagnosis.Methods: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and six, twelve, twenty-four, and sixty (T6 to T60) months post-diagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population.Results: In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared to men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared to the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6.Conclusions: Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at six months post-diagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.

Purpose: Higher dairy consumption is associated with a lower risk of colorectal cancer (CRC), but no studies thus far have investigated its relation with recurrence in CRC. Few studies have investigated total dairy in relation to mortality in CRC, and yielded inconsistent results. Methods: In this prospective cohort study, people newly diagnosed with stage I-III CRC filled out a food frequency questionnaire at diagnosis (n = 1812) and six months after diagnosis (n = 1672). We examined associations between pre- and post-diagnostic intake of total dairy, low-fat dairy, high-fat dairy, milk, yoghurt, and cheese with recurrence and all-cause mortality using multivariable Cox proportional hazard models and restricted cubic splines (RCS). Results: A total of 176 recurrences and 301 deaths occurred during a median follow-up of 3.0 and 5.9 years, respectively. Before diagnosis, a higher low-fat dairy intake was associated with a lower risk of recurrence (HRQ4vsQ1: 0.42, 95% CI 0.26–0.67; PRCS: 0.008) and all-cause mortality (HRQ4vsQ1: 0.58, 95% CI 0.41–0.81; PRCS < 0.001), whereas a higher high-fat dairy consumption tended to be associated with an increased all-cause mortality risk (HRQ4vsQ1: 1.41, 95% CI 0.98–2.01; PRCS: 0.030). After diagnosis, only the associations between low- and high-fat dairy in relation to all-cause mortality remained. Conclusions: This study demonstrated that higher pre- and post-diagnostic intakes of low-fat dairy were associated with a reduced all-cause mortality risk in people with stage I-III CRC, whereas higher intakes of high-fat dairy were associated with an increased all-cause mortality risk. Also, a higher pre-diagnostic low-fat dairy intake was associated with a reduced risk of recurrence. Trial registration: Clinical Trials.gov identifier: NCT03191110.

Importance: Postoperative complications are associated with increased morbidity and mortality among patients with colorectal cancer. As a modifiable factor associated with gut health, dietary fiber intake is of interest with regard to the risk of complications after surgery for colorectal cancer. Objective: To examine the association between preoperative dietary fiber intake and risk of complications after surgery for colorectal cancer. Design, Setting, and Participants: This cohort study used data from the Colorectal Longitudinal, Observational Study on Nutritional and Lifestyle Factors (COLON) study, which recruited adult patients with colorectal cancer at any stage at diagnosis from 11 hospitals in the Netherlands between August 2010 and December 2017. The present study included patients with stage I to IV colorectal cancer who underwent elective abdominal surgery. Data were analyzed between December 2019 and September 2020. Exposures: Habitual dietary fiber intake was assessed at diagnosis using a 204-item food frequency questionnaire. Main Outcomes and Measures: Any complications, surgical complications, and anastomotic leakage occurring during the 30 days after surgery for colorectal cancer. The association between fiber intake and risk of postoperative complications was assessed using logistic regression analyses. Additional analyses stratified by sex, tumor location, and fiber source were performed. Results: Among the 1399 patients included in the analysis, the median age at inclusion was 66 years (interquartile range, 61-72 years) and 896 (64%) were men. Any complications occurred in 397 patients (28%), and surgical complications occurred in 235 patients (17%). Of 1237 patients with an anastomosis, 67 (5%) experienced anastomotic leakage. Higher dietary fiber intake (per 10 g per day) was associated with a lower risk of any complications (odds ratio [OR], 0.75; 95% CI, 0.62-0.92) and surgical complications (OR, 0.76; 95% CI, 0.60-0.97), whereas no associati

Current lifestyle recommendations for cancer survivors are the same as those for the general public to decrease their risk of cancer. However, it is unclear which lifestyle behaviors are most important for prognosis. We aimed to identify which lifestyle behaviors were most important regarding colorectal cancer (CRC) recurrence and all-cause mortality with a data-driven method. The study consisted of 1180 newly diagnosed stage I–III CRC patients from a prospective cohort study. Lifestyle behaviors included in the current recommendations, as well as additional lifestyle behaviors related to diet, physical activity, adiposity, alcohol use, and smoking were assessed six months after diagnosis. These behaviors were simultaneously analyzed as potential predictors of recurrence or all-cause mortality with Random Survival Forests (RSFs). We observed 148 recurrences during 2.6-year median follow-up and 152 deaths during 4.8-year median follow-up. Higher intakes of sugary drinks were associated with increased recurrence risk. For all-cause mortality, fruit and vegetable, liquid fat and oil, and animal protein intake were identified as the most important lifestyle behaviors. These behaviors showed non-linear associations with all-cause mortality. Our exploratory RSF findings give new ideas on potential associations between certain lifestyle behaviors and CRC prognosis that still need to be confirmed in other cohorts of CRC survivors.

Background: Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown. Methods: Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival. Results: No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n=296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival. Conclusions: Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence.

Background: The influence of physical activity on patient-reported recovery of physical functioning after colorectal cancer (CRC) surgery is unknown. Therefore, we studied recovery of physical functioning after hospital discharge by (a) a relative increase in physical activity level and (b) absolute activity levels before and after surgery. Methods: We included 327 incident CRC patients (stages I-III) from a prospective observational study. Patients completed questionnaires that assessed physical functioning and moderate-to-vigorous physical activity shortly after diagnosis and 6 months later. Cox regression models were used to calculate prevalence ratios (PRs) of no recovery of physical functioning. All PRs were adjusted for age, sex, physical functioning before surgery, stage of disease, ostomy and body mass index. Results: At 6 months post-diagnosis 54% of CRC patients had not recovered to pre-operative physical functioning. Patients who increased their activity by at least 60 min/week were 43% more likely to recover physical function (adjusted PR 0.57 95%CI 0.39-0.82), compared with those with stable activity levels. Higher post-surgery levels of physical activity were also positively associated with recovery (P for trend = 0.01). In contrast, activity level before surgery was not associated with recovery (P for trend = 0.24). Conclusions: At 6 month post-diagnosis, about half of CRC patients had not recovered to preoperative functioning. An increase in moderate-to-vigorous physical activity after CRC surgery was associated with enhanced recovery of physical functioning. This benefit was seen regardless of physical activity level before surgery. These associations provide evidence to further explore connections between physical activity and recovery from CRC surgery after discharge from the hospital.