Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in ...assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were ed from questionnaires and medical records.
What's new?
Colorectal cancer exhibits certain characteristic changes in metabolic pathways. To expand upon previous findings, these authors performed a discovery‐replication study using two large independent study populations from different countries, Germany and Austria. They tested metabolic profiles of cancer patients and controls, identifying 691 statistically significant features in the discovery cohort. Testing the second cohort narrowed it to 97. These corresponded to 28 metabolites, of which 15 could be identified. It will be useful to go forward with prospective analysis on these 15 metabolites, to determine whether they have predictive or prognostic value.
The population of colorectal cancer (CRC) survivors is growing and many survivors experience deteriorated health‐related quality of life (HRQoL) in both early and late post‐treatment phases. ...Identification of CRC survivors at risk for HRQoL deterioration can be improved by using prediction models. However, such models are currently not available for oncology practice. As a starting point for developing prediction models of HRQoL for CRC survivors, a comprehensive overview of potential candidate HRQoL predictors is necessary. Therefore, a systematic literature review was conducted to identify candidate predictors of HRQoL of CRC survivors. Original research articles on associations of biopsychosocial factors with HRQoL of CRC survivors were searched in PubMed, Embase, and Google Scholar. Two independent reviewers assessed eligibility and selected articles for inclusion (N = 53). Strength of evidence for candidate HRQoL predictors was graded according to predefined methodological criteria. The World Health Organization's International Classification of Functioning, Disability and Health (ICF) was used to develop a biopsychosocial framework in which identified candidate HRQoL predictors were mapped across the main domains of the ICF: health condition, body structures and functions, activities, participation, and personal and environmental factors. The developed biopsychosocial ICF framework serves as a basis for selecting candidate HRQoL predictors, thereby providing conceptual guidance for developing comprehensive, evidence‐based prediction models of HRQoL for CRC survivors. Such models are useful in clinical oncology practice to aid in identifying individual CRC survivors at risk for HRQoL deterioration and could also provide potential targets for a biopsychosocial intervention aimed at safeguarding the HRQoL of at‐risk individuals.
Implications for Practice:
More and more people now survive a diagnosis of colorectal cancer. The quality of life of these cancer survivors is threatened by health problems persisting for years after diagnosis and treatment. Early identification of survivors at risk of experiencing low quality of life in the future is thus important for taking preventive measures. Clinical prediction models are tools that can help oncologists identify at‐risk individuals. However, such models are currently not available for clinical oncology practice. This systematic review outlines candidate predictors of low quality of life of colorectal cancer survivors, providing a firm conceptual basis for developing prediction models.
摘要
结直肠癌 （CRC） 幸存者人群正在日益增加, 许多幸存者在治疗后早期和远期发生了健康相关生活质量 （HRQoL） 恶化。使用预测模型有可能改善对有 HRQoL 恶化风险的 CRC 幸存者的鉴别。但是目前肿瘤学临床实践中还没有这类模型。对可能的备选 HRQoL 预测因素进行全面综述是开发 CRC 幸存者 HRQoL 模型所必要的第一步。因此, 我们对鉴别 CRC 幸存者的备选 HRQoL 预测因素进行了系统性文献综述。我们在 PubMed、Embase 和 Google Scholar 对与 CRC 幸存者 HRQoL 相关的生物心理社会学因素的原创研究文献进行了检索。由 2 名独立评审员对文章的合格性进行评估, 并且选择入选文献 （N=53）。根据预先定义的方法学标准对备选 HRQoL 预测因素的证据强度进行评级。使用世界卫生组织颁布的国际功能、残疾和健康分类 （ICF） 建立生物心理社会学框架, 鉴别出来的备选 HRQoL 预测因素分布在 ICF 的主要领域中: 健康状况、身体结构和功能、活动程度、参与性, 以及个人和环境因素。建立的生物心理社会学 ICF 框架可作为选择备选 HRQoL 预测因素的基础, 从而为建立 CRC 幸存者 HRQoL 的综合循证预测模型提供概念性指导。这类模型对肿瘤学临床实践十分有用, 可有助于鉴别出存在 HRQoL 恶化危险因素的 CRC 幸存者个体, 同时, 就为 HRQoL 在险个体提供保护措施而言, 该模型也能给出实施生物心理社会学干预的可能靶点。The Oncologist 2016;21:433–452
对临床实践的提示: 如今, 越来越多的确诊结直肠癌患者能够存活下来。而诊断和治疗后持续存在的健康问题年复一年地威胁着这些癌症幸存者的生活质量。因此, 在未来早期鉴别出存在生活质量降低风险的幸存者对于采取预防性措施十分重要。临床预测模型是能够帮助肿瘤科医生鉴别在险个体的工具。然而目前肿瘤学的临床实践中还没有这类模型。本项系统综述概略地给出了结直肠癌幸存者低生活质量的备选危险因素, 为建立预测模型提供了坚实的理论依据。
A systematic literature review was conducted to identify candidate predictors of health‐related quality of life (HRQoL) of colorectal cancer (CRC) survivors that could be used to develop prediction models of HRQoL deterioration. A model of HRQoL was developed based on the biopsychosocial framework of the International Classification of Functioning, Disability and Health, which serves as a basis for selecting candidate HRQoL predictors and thereby provides conceptual guidance for developing comprehensive, evidence‐based prediction models of HRQoL for CRC survivors.
We previously demonstrated that intake of low‐fat dairy, but not high‐fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, ...primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I–III CRC enabled these subgroup analyses. Participants completed a food frequency questionnaire at diagnosis (n = 2283). We examined associations between low‐ and high‐fat dairy intake and recurrence risk using multivariable Cox proportional hazard models, stratified by sex, and primary tumour location (colon and rectum), and disease stage (I/II and III). Upper quartiles were compared to lower quartiles of intake, and recurrence was defined as a locoregional recurrence and/or metastasis. During a median follow‐up of 5.0 years, 331 recurrences were detected. A higher intake of low‐fat dairy was associated with a reduced risk of recurrence (hazard ratio HR: 0.60, 95% confidence interval CI: 0.43–0.83), which seemed more pronounced in men (HR: 0.51, 95% CI: 0.34–0.77) than in women (HR: 0.84, 95% CI: 0.47–1.49). A higher intake of high‐fat dairy was associated with an increased risk of recurrence in participants with colon cancer (HR: 1.60, 95% CI: 1.03–2.50), but not rectal cancer (HR: 0.88, 95% CI: 0.54–1.45). No differences in associations were observed between strata of disease stage. Concluding, our findings imply that dietary advice regarding low‐fat dairy intake may be especially important for men with CRC, and that dietary advice regarding high‐fat dairy intake may be specifically important in people with colon cancer.
What's new?
There is strong evidence that dairy intake is associated with a reduced risk of developing colorectal cancer. However, its relation to the risk of colorectal cancer recurrence remains unclear. Combining data from two prospective cohort studies of patients with stage I–III colorectal cancer, this study found that a higher intake of low‐fat dairy was associated with a reduced risk of recurrence in men, where as a higher intake of high‐fat dairy was associated with an increased risk of recurrence in people with colon cancer. With a global transition towards more plant‐based diets and increasing numbers of colorectal cancer survivors, the findings may contribute to more personalised dietary guidelines.
Abstract
Colorectal cancer (CRC) survivors need evidence-based guidelines pertaining to post-treatment body composition, which could benefit health-related quality of life (HRQoL). We aimed to ...describe the course of several body composition measures, and to assess longitudinal associations of these measures with HRQoL, fatigue and chemotherapy-induced peripheral neuropathy (CIPN). In a prospective cohort among stage I–III CRC survivors (n = 459), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Body mass index (BMI), waist circumference and fat percentage were assessed as measures of adiposity, and muscle arm circumference and handgrip strength as measures of muscle mass and function. We applied linear mixed-models to describe changes in body composition over time and to analyze overall longitudinal associations. Of included participants, 44% was overweight and 31% was obese at diagnosis. All body composition measures followed similar trends, decreasing from diagnosis to 6 weeks and then increasing up to 24 months post-treatment. In confounder-adjusted mixed models, increases in adipose tissue and muscle function were longitudinally associated with better HRQoL and less fatigue, regardless of pre-treatment body composition. With regards to improving HRQoL, decreasing fatigue and CIPN, clinical practice should also focus on restoring body tissues after CRC treatment.
Trial registration:
NTR7099.
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.
What's new?
Although existing evidence suggests that coffee consumption may lower colorectal cancer risk, the association with colorectal cancer prognosis remains unclear. This large prospective study of stage I–III patients in a country with a relatively high coffee intake revealed a strong inverse association between coffee consumption and colorectal cancer recurrence. The association between coffee consumption and all‐cause mortality in colorectal cancer patients was nonlinear, suggesting an optimal intake of three to five cups per day. The findings could potentially inform future intervention studies as well as dietary guidelines for colorectal cancer patients.
Higher concentrations of 25-hydroxyvitamin D3 25(OH)D3 at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in ...vitamin D metabolism.
We aimed to investigate 25(OH)D3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality.
The study population included 1169 newly diagnosed stage I–III CRC patients from 2 prospective cohorts. Associations between 25(OH)D3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another.
Serum 25(OH)D3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 vs. Q1: 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. Q1: 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (<50 nmol/L) and had a low magnesium intake. No interactions between calcium and vitamin D in relation to all-cause mortality were observed.
Our findings suggest that the presence of an adequate status of 25(OH)D3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings. The COLON study was registered at clinicaltrials.gov as NCT03191110. The EnCoRe study was registered at trialregister.nl as NTR7099.
The increasing colorectal cancer (CRC) survivor population highlights the need for dietary recommendations in order to enhance health-related quality of life (HRQoL) and alleviate symptoms of ...fatigue, chemotherapy-induced peripheral neuropathy (CIPN), and gastrointestinal problems.
Because of the therapeutic potential of dietary fiber on the gut, we aim to assess longitudinal associations of postdiagnostic dietary fiber, fruit, and vegetable intake, a major source of dietary fiber, with HRQoL, fatigue, CIPN, and gastrointestinal symptoms in CRC survivors from 6 wk to 24 mo posttreatment.
In a prospective cohort among stage I–III CRC survivors (n = 459), 5 repeated study measurements between diagnosis and 24 mo posttreatment were executed. Dietary fiber intake and fruit and vegetable intake were measured by 7-d dietary records. HRQoL, fatigue, CIPN, and gastrointestinal symptoms were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyze longitudinal associations from 6 wk until 24 mo posttreatment and used hybrid models to disentangle the overall association into intraindividual changes and interindividual differences over time.
Higher dietary fiber intake and fruit and vegetable intake were longitudinally associated with statistically significant better physical functioning and less fatigue. Intraindividual analyses showed that an increase of 10 g/d in dietary fiber within individuals over time was associated with better physical functioning (β: 2.3; 95% CI: 0.1, 4.4), role functioning (ability to perform daily activities; 5.9; 1.5, 10.3), and less fatigue (−4.1; −7.7, −0.5). An average increase in fruit and vegetable intake of 100 g/d between individuals over time was predominantly associated with less fatigue (−2.2; −4.2, −0.3). No associations were found with CIPN and gastrointestinal symptoms.
Our results suggest that increasing dietary fiber, fruit, and vegetable intake is related to better physical and role functioning and less fatigue in the first 2 y after the end of treatment for CRC.
Aim
Colorectal anastomotic leakage (AL) is a serious complication. Studies on the impact of AL on health‐related quality of life (HRQoL) are scarce. We aimed to investigate the association between AL ...and HRQoL in colorectal cancer patients up to 2 years after diagnosis, and to evaluate whether AL is associated with a clinically relevant decrease in HRQoL over time.
Methods
Patients diagnosed with Stage I–III colorectal cancer undergoing elective surgical resection with primary anastomosis between 2010 and 2017 were included. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, represented by the summary score, and analysed at diagnosis and at 6 months and 2 years post‐diagnosis. Multivariable linear regression was performed to assess the association between AL and HRQoL, while multivariable logistic regression was used to investigate the association between AL and a clinically relevant HRQoL decrease (≥10 points) during follow‐up compared to the time of diagnosis.
Results
In total, 1197 patients were included of whom 63 (5%) developed AL. AL was not associated with HRQoL at 6 months post‐diagnosis nor at 2 years post‐diagnosis. However, having AL was associated with an increased risk of a clinically relevant decrease in HRQoL at 6 months post‐diagnosis (OR 3.65, 95% CI 1.62–8.21) but not at 2 years after diagnosis (OR 1.91, 95% CI 0.62–5.93).
Conclusion
Although AL was not associated with HRQoL at 6 months or 2 years post‐diagnosis, AL was a determinant of a clinically relevant decrease in HRQoL at 6 months after diagnosis. Future work should identify feasible and effective strategies to prevent declines in QoL in this patient population.
An unhealthy lifestyle is associated with the risk of colorectal cancer (CRC), but it is unclear whether overall lifestyle after a CRC diagnosis is associated with risks of recurrence and mortality.
...To examine associations between postdiagnosis lifestyle and changes in lifestyle after a CRC diagnosis with risks of CRC recurrence and all-cause mortality.
The study population included 1425 newly diagnosed, stage I–III CRC patients from 2 prospective cohort studies enrolled between 2010 and 2016. Lifestyle, including BMI, physical activity, diet, and alcohol intake, was assessed at diagnosis and at 6 months postdiagnosis. We assigned lifestyle scores based on concordance with 2 sets of cancer prevention guidelines—from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and the American Cancer Society (ACS)—and national disease prevention guidelines. Higher scores indicate healthier lifestyles. We computed adjusted HRs and 95% CIs using Cox regression.
We observed 164 recurrences during a 2.8-year median follow-up and 171 deaths during a 4.4-year median follow-up. No associations were observed for CRC recurrence. A lifestyle more consistent with the ACS recommendations was associated with a lower all-cause mortality risk (HR per +1 SD, 0.85; 95% CI: 0.73–0.995). The same tendency was observed for higher WCRF/AICR (HR, 0.92; 95% CI: 0.78–1.08) and national (HR, 0.90; 95% CI: 0.77–1.05) lifestyle scores, although these associations were statistically nonsignificant. Generally, no statistically significant associations were observed for BMI, physical activity, diet, or alcohol. Improving one’s lifestyle after diagnosis (+1 SD) was associated with a lower all-cause mortality risk for the ACS (HR, 0.80; 95% CI: 0.67–0.96) and national (HR, 0.84; 95% CI: 0.70–0.999) scores, yet was statistically nonsignificant for the WCRF/AICR score (HR, 0.94; 95% CI: 0.78–1.13).
A healthy lifestyle after CRC diagnosis and improvements therein were not associated with the risk of CRC recurrence, but were associated with a decreased all-cause mortality risk.
▪
There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and ...quality of life. This paper describes the background and design of the "COlorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life" - COLON - study. The main aim of this study is to assess associations of diet and other lifestyle factors, with colorectal cancer recurrence, survival and quality of life. We extensively investigate diet and lifestyle of colorectal cancer patients at diagnosis and during the following years; this design paper focusses on the initial exposures of interest: diet and dietary supplement use, body composition, nutrient status (e.g. vitamin D), and composition of the gut microbiota.
The COLON study is a multi-centre prospective cohort study among at least 1,000 incident colorectal cancer patients recruited from 11 hospitals in the Netherlands. Patients with colorectal cancer are invited upon diagnosis. Upon recruitment, after 6 months, 2 years and 5 years, patients fill out food-frequency questionnaires; questionnaires about dietary supplement use, physical activity, weight, height, and quality of life; and donate blood samples. Diagnostic CT-scans are collected to assess cross-sectional areas of skeletal muscle, subcutaneous fat, visceral fat and intermuscular fat, and to assess muscle attenuation. Blood samples are biobanked to facilitate future analyse of biomarkers, nutrients, DNA etc. Analysis of serum 25-hydroxy vitamin D levels, and analysis of metabolomic profiles are scheduled. A subgroup of patients with colon cancer is asked to provide faecal samples before and at several time points after colon resection to study changes in gut microbiota during treatment. For all patients, information on vital status is retrieved by linkage with national registries. Information on clinical characteristics is gathered from linkage with the Netherlands Cancer Registry and with hospital databases. Hazards ratios will be calculated for dietary and lifestyle factors at diagnosis in relation to recurrence and survival. Repeated measures analyses will be performed to assess changes over time in dietary and other factors in relation to recurrence and survival.
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