A systematic review of the association between physical activity and colorectal cancer risk

This review evaluated the strength of the evidence for a causal relationship between physical activity (PA) and colorectal cancer (CRC). A systematic review of databases through February 2008 was conducted to identify studies that assessed the association between total or recreational PA and incidence or mortality of CRC (including CRC, rectal cancer, colon cancer, and proximal or distal colon cancer). Studies were evaluated for significant associations between PA and risk of CRC endpoints and for evidence of dose–response relationships in the highest quality studies. Twenty cohort studies were evaluated; 11 were high-quality. Fifty percent of all studies and 64%of highest quality studies reported at least one significant association between PA and risk of a CRC endpoint (Po0.05).However, only 28%of all analyses (31% of analyses of highest quality studies) were significant (Po0.05). Only 40% of analyses of highest quality studies resulted in a significant P for trend (Po0.05); however, a non-significant inverse linear association between PA and colon cancer riskwas apparent.Heterogeneity in the evidence from all studies and from the highest quality studies was evident. Evidence from cohort studies is not sufficient to claim a convincing relationship exists between PA and CRC risk.

Colorectal cancer survivors’ exercise experiences and preferences : qualitative findings from an exercise rehabilitation programme immediately after chemotherapy

Little is known about cancer survivors’ experiences with and preferences for exercise programmes offered during rehabilitation (immediately after cancer treatment). This study documented colorectal cancer survivors’ experiences in an exercise rehabilitation programme and their preferences for programme content and delivery. At the completion of 12-weeks of supervised exercise, 10 participants took part in one-on-one semi-structured interviews. Data from these interviews were coded, and themes were identified using qualitative software. Key findings were that most participants experienced improvements in treatment symptoms, including reduced fatigue and increased energy and confidence to do activities of daily living. They also reported that interactions with the exercise trainer and a flexible programme delivery were important aspects of the intervention. Most participants reported that they preferred having a choice of exercise, starting to exercise within a month after completing treatment, having supervision and maintaining a one-on-one format. Frustrations included scheduling conflicts and a lack of a transition out of the programme. The findings indicate that colorectal cancers experience benefits from exercise offered immediately after treatment and prefer individual attention from exercise staff. They further indicate directions for the implementation of future exercise programmes with this population.

Lifestyle factors associated concurrently and prospectively with co-morbid cardiovascular disease in a population-based cohort of colorectal cancer survivors

Aims To assess self-reported lifetime prevalence of cardiovascular disease (CVD) among colorectal cancer survivors, and examine the cross-sectional and prospective associations of lifestyle factors with co-morbid CVD. Methods Colorectal cancer survivors were recruited (n = 1966). Data were collected at approximately 5, 12, 24 and 36 months post-diagnosis. Cross-sectional findings included six CVD categories (hypercholesterolaemia, hypertension, diabetes, heart failure, kidney disease and ischaemic heart disease (IHD)) at 5 months post-diagnosis. Longitudinal outcomes included the probability of developing (de novo) co-morbid CVD by 36 months post-diagnosis. Lifestyle factors included body mass index, physical activity, television (TV) viewing, alcohol consumption and smoking. Results Co-morbid CVD prevalence at 5 months post-diagnosis was 59%, and 16% of participants with no known CVD at the baseline reported de novo CVD by 36 months. Obesity at the baseline predicted de novo hypertension (odds ratio [OR] = 2.20, 95% confidence intervals [CI] = 1.09, 4.45) and de novo diabetes (OR = 6.55, 95% CI = 2.19, 19.53). Participants watching >4 h of TV/d at the baseline (compared with <2 h/d) were more likely to develop ischaemic heart disease by 36 months (OR = 5.51, 95% CI = 1.86, 16.34). Conclusion Overweight colorectal cancer survivors were more likely to suffer from co-morbid CVD. Interventions focusing on weight management and other modifiable lifestyle factors may reduce functional decline and improve survival.

Randomised controlled trial of a supervised exercise rehabilitation program for colorectal cancer survivors immediately after chemotherapy: study protocol

Background Colorectal cancer (CRC) diagnosis and the ensuing treatments can have a substantial impact on the physical and psychological health of survivors. As the number of CRC survivors increases, so too does the need to develop viable rehabilitation programs to help these survivors return to good health as quickly as possible. Exercise has the potential to address many of the adverse effects of CRC treatment; however, to date, the role of exercise in the rehabilitation of cancer patients immediately after the completion of treatment has received limited research attention. This paper presents the design of a randomised controlled trial which will evaluate the feasibility and efficacy of a 12-week supervised aerobic exercise program (ImPACT Program) on the physiological and psychological markers of rehabilitation, in addition to biomarkers of standard haematological outcomes and the IGF axis. Methods/Design Forty CRC patients will be recruited through oncology clinics and randomised to an exercise group or a usual care control group. Baseline assessment will take place within 4 weeks of the patient completing adjuvant chemotherapy treatment. The exercise program for patients in the intervention group will commence a week after the baseline assessment. The program consists of three supervised moderate-intensity aerobic exercise sessions per week for 12 weeks. All participants will have assessments at baseline (0 wks), mid-intervention (6 wks), post-intervention (12 wks) and at a 6-week follow-up (18 wks). Outcome measures include cardio-respiratory fitness, biomarkers associated with health and survival, and indices of fatigue and quality of life. Process measures are participants' acceptability of, adherence to, and compliance with the exercise program, in addition to the safety of the program. Discussion The results of this study will provide valuable insight into the role of supervised exercise in improving life after CRC. Additionally, process analyses will inform the feasibility of implementing the program in a population of CRC patients immediately after completing chemotherapy.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

The Working After Cancer Study (WACS): a population-based study of middle-aged workers diagnosed with colorectal cancer and their return to work experiences

Background The number of middle-aged working individuals being diagnosed with cancer is increasing and so too will disruptions to their employment. The aim of the Working After Cancer Study is to examine the changes to work participation in the 12 months following a diagnosis of primary colorectal cancer. The study will identify barriers to work resumption, describe limitations on workforce participation, and evaluate the influence of these factors on health-related quality of life. Methods/Design An observational population-based study has been designed involving 260 adults newly-diagnosed with colorectal cancer between January 2010 and September 2011 and who were in paid employment at the time they were diagnosed. These cancer cases will be compared to a nationally representative comparison group of 520 adults with no history of cancer from the general population. Eligible cases will have a histologically confirmed diagnosis of colorectal cancer and will be identified through the Queensland Cancer Registry. Data on the comparison group will be drawn from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data collection for the cancer group will occur at 6 and 12 months after diagnosis, with work questions also asked about the time of diagnosis, while retrospective data on the comparison group will be come from HILDA Waves 2009 and 2010. Using validated instruments administered via telephone and postal surveys, data will be collected on socio-demographic factors, work status and circumstances, and health-related quality of life (HRQoL) for both groups while the cases will have additional data collected on cancer treatment and symptoms, work productivity and cancer-related HRQoL. Primary outcomes include change in work participation at 12 months, time to work re-entry, work limitations and change in HRQoL status. Discussion This study will address the reasons for work cessation after cancer, the mechanisms people use to remain working and existing workplace support structures and the implications for individuals, families and workplaces. It may also provide key information for governments on productivity losses.

Geographic remoteness, area-level socioeconomic disadvantage and inequalities in colorectal cancer survival in Queensland : a multilevel analysis

Background To explore the impact of geographical remoteness and area-level socioeconomic disadvantage on colorectal cancer (CRC) survival. Methods Multilevel logistic regression and Markov chain Monte Carlo simulations were used to analyze geographical variations in five-year all-cause and CRC-specific survival across 478 regions in Queensland Australia for 22,727 CRC cases aged 20–84 years diagnosed from 1997–2007. Results Area-level disadvantage and geographic remoteness were independently associated with CRC survival. After full multivariate adjustment (both levels), patients from remote (odds Ratio [OR]: 1.24, 95%CrI: 1.07-1.42) and more disadvantaged quintiles (OR = 1.12, 1.15, 1.20, 1.23 for Quintiles 4, 3, 2 and 1 respectively) had lower CRC-specific survival than major cities and least disadvantaged areas. Similar associations were found for all-cause survival. Area disadvantage accounted for a substantial amount of the all-cause variation between areas. Conclusions We have demonstrated that the area-level inequalities in survival of colorectal cancer patients cannot be explained by the measured individual-level characteristics of the patients or their cancer and remain after adjusting for cancer stage. Further research is urgently needed to clarify the factors that underlie the survival differences, including the importance of geographical differences in clinical management of CRC.

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.