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Background: Pre-diagnostic physical activity may lower the risk for developing colon cancer and is potentially associatedwith improved prognosis when diagnosed with colorectal cancer. Body composition and immune cell infiltration in the tumour microenvironment are also associated with prognosis in colorectal cancer. The physical activity guidelines are the same in colorectal cancer patients as in the healthy population and the national health care programme for colorectal cancer in Sweden recommends individualised support for physical activity to all patients.

Aims: The overall aim of this thesis was to evaluate pre-diagnostic physical activity, assessed using self-reported questionnaire, from physical tests, by using an accelerometer, using interviews and its relationship with colorectal cancer with regard to immune cell infiltration of the tumour, body composition, and the patient’s own experiences.

Results: Study I: Pre-diagnostic physical exercise more than three times a week was associated with increased numbers of cytotoxic T cells in the tumour front (OR 2.91, 95% CI 1.25-6.75) and centre (OR 2.92, 95% CI1.31-6.50)

Study II: Low pre-diagnostic physical exercise was not associated with sarcopenia, i.e. low muscle mass (OR1.37, 95% CI 0.86-2.19) nor myosteatosis, i.e. low muscle quality (OR 0.95, 95% CI 0.59-1.51) at the time of colorectal cancer diagnosis

Study III: After adjusting for multiple testing no significant results were seen in either the descriptive statistics or in the logistic regression model adjusted for age and sex.

Study IV: Various experiences were expressed towards physical activity described in three main categories “I’ll fight the cancer and come out stronger”; “the diagnosis makes no difference”; and “the cancer is an obstacle for physical activity”.

Conclusions: Self-reported physical exercise may be associated with increased numbers of cytotoxic T cells in the microenvironment of colorectal cancer. However, this was neither confirmed nor rejected when assessing physical activity and fitness more objectively in a smaller cohort. Little physical exercise in middle age was not associated with sarcopenia or myosteatosis at the time of colorectal cancer diagnosis but when present together, cancer-specific mortality risk was increased. Physically active individuals have a wide spectrum of attitudes and experiences toward physical activity when diagnosed with colon cancer.

Purpose: Sarcopenia and myosteatosis, quantified via computed tomography (CT), are associated with poor colorectal cancer outcomes. These body composition estimates can be influenced by physical exercise. We explored the correlation between pre-diagnostic physical exercise, body composition close to diagnosis, and the combined prognosis impact of these factors.

Methods: We studied 519 stage I–III colorectal cancer (CRC) cases diagnosed 2000–2016 with pre-diagnostic self-reported recreational physical exercise data collected in the prospective, population-based Northern Sweden Health and Disease Study, and CT-estimated skeletal muscle index (SMI) or skeletal muscle density (SMD). Risk estimates were calculated by multivariable logistic regression and Cox proportional hazards models.

Results: No association was seen between low pre-diagnostic physical exercise and sarcopenia/myosteatosis in the multivariable model adjusted for age, sex, educational level, tumor stage, and tumor location. In multivariable Cox regression models, the combination of low pre-diagnostic physical exercise and either sarcopenia or myosteatosis at the time of diagnosis was associated with cancer-specific mortality compared to the reference group of high physical exercise combined with no sarcopenia/myosteatosis (adjusted HR 1.94 95% CI 1.00–3.76 for sarcopenia and adjusted HR 2.39 95% CI 1.16–4.94 for myosteatosis).

Conclusions: The combined presence of low pre-diagnostic physical exercise and sarcopenia or myosteatosis was associated with increased CRC-specific mortality. Despite the positive effect on prognosis, physical exercise did not alter body composition estimates at diagnosis, which could indicate attenuation from other factors.

BACKGROUND: Physical activity improves survival, reduces postoperative complications, and reduces the risk of developing colon cancer. It is important to maintain physical activity after receiving a diagnosis of colon cancer to improve postoperative recovery. Individuals who are physically active and diagnosed with colon cancer presumably have different motivations to maintain physical activity compared to their sedentary counterparts.

OBJECTIVE: Enlighten how the diagnosis of colon cancer might affect physically active individuals in their attitude and experiences towards physical activity.

METHODS: A qualitative study using content analysis was conducted in northern Sweden based on semi-structured telephone interviews of twenty patients diagnosed with colon cancer. All participants met the recommendations for physical activity issued by the World Health Organization.

RESULTS: Participants were between 50 and 88 years and 50% were male. Three main categories were identified: I'll fight the cancer and come out stronger; The diagnosis makes no difference; and The diagnosis is an obstacle for physical activity. These main categories represent the ways the individuals reacted to the diagnosis of colon cancer regarding their physical activity.

CONCLUSION: Attitudes to and experience of physical activity after colon cancer diagnosis varied from a will to increase physical activity and fight the cancer, to the diagnosis putting a stop to physical activity. It is important that healthcare professionals recommend physical activity even in already physically active individuals, to encourage continued physical activity after diagnosis of colon cancer.

Introduction: Physical activity is associated not only with a decreased risk of developing colorectal cancer but also with improved survival. One putative mechanism is the infiltration of immune cells in the tumor microenvironment. Experimental findings suggest that physical activity may mobilize immune cells to the tumor. We hypothesized that higher levels of physical activity prior to colorectal cancer diagnosis are associated with higher densities of tumor-infiltrating T-lymphocytes in colorectal cancer patients.

Method: The study setting was a northern Swedish population-based cohort, including 109792 participants with prospectively collected health- and lifestyle-related data. For 592 participants who later developed colorectal cancer, archival tumor tissue samples were used to assess the density of CD3⁺ and CD8⁺ cytotoxic T-cells by immunohistochemistry. Odds ratios for associations between self-reported, pre-diagnostic recreational physical activity and immune-cell infiltration were estimated by ordinal logistic regression.

Results: Recreational physical activity >3 times per week was associated with a higher density of CD8⁺ T-cells in the tumor front and center compared to participants reporting no recreational physical activity. Odds ratios were 2.77 (95% CI 1.21-6.35) and 2.85 (95% CI 1.28-6.33) for the tumor front and center, respectively, after adjustment for sex, age at diagnosis, and tumor stage. The risk estimates were consistent after additional adjustment for several potential confounders. For CD3 no clear associations were found.

Conclusion: Physical activity may promote the infiltration of CD8⁺ immune cells in the tumor microenvironment of colorectal cancer.

Impact: The study provides some evidence on how physical activity may alter the prognosis in colorectal cancer.

Background: Statins are the backbone of lipid-lowering therapy and are among the most commonly prescribed drugs in the elderly population in Sweden today. Colorectal cancer is the second most common cancer in men and women, after prostate and breast cancer, respectively, with a median age of 72 years at diagnosis. Statins induce mitochondrial damage leading to accumulation of reactive oxygen species in the cell. Reactive oxygen species can cause mutations in mitochondrial as well as nuclear DNA leading to the development of cancer. Our hypothesis was that statins increase the risk for colorectal cancer.

Methods: A case study was performed on consecutive cases of colorectal cancer diagnosed at Norrlands University Hospital (NUS) in Umeå between 2012 and 2015 (n = 325). Patients diagnosed with diabetes mellitus type II (DM II n = 65) were excluded in the primary endpoint analysis (occurrence of colorectal cancer). As control, three databases were used to create an age-matched population in order to calculate the proportion of inhabitants using statins in the county of Västerbotten, Sweden. A secondary endpoint was cancer-specific survival among our study group of colorectal cancer patients, including those with DM II, investigating whether there was a difference if the patient was a 'recent' statin user or not at the time of diagnosis.

Results: Statin use at the time of colorectal cancer diagnosis in the study group was 23.8%. The corresponding figure in an age-matched population in Västerbotten was 24.6%. Using a one-proportional one-sided z test, there was no significant difference between these (23.8%, 95% CI 18.6-29.0%, p = 0.601). When comparing groups 20-64 years of age, the difference was greater with recent statin use in 17.8% in the study population and 11.9% in Västerbotten (17.8%, 95% CI 9.0-26.6%, p = 0.059). When considering cancer-specific survival, no significant difference in survival was seen when comparing 'former/never' statin users as reference category with 'recent' users diagnosed with colorectal cancer (HR 1.39, 95% CI 0.89-2.16).

Conclusions: No significant increase in risk for developing colorectal cancer among patients (type II diabetics excluded) medicated with statins was found. We found no correlation between 'recent' statin use at the time of diagnosis and cancer-specific survival.

Background: Both physical activity and immune cell infiltration of the tumor microenvironment are associated with improved prognosis in colon cancer. There is also evidence that physical activity may mobilize immune cells against colon tumors. One possible mechanism behind the positive effect of physical activity on colon cancer prognosis could thus be increased immune cell infiltration of the tumor microenvironment. There are few previous studies examining this association, and none has included an objective assessment of physical activity and fitness.

Methods: This was a cohort study on 69 patients diagnosed with colon cancer stages I-III, all eligible for curative surgery, and with no previous treatment. Prior to surgery, the participants underwent physical tests, dual-energy X-ray absorptiometry, and wore an accelerometer to quantify their physical activity and physical fitness. Tumor infiltration by cytotoxic T cells, T-helper 1 cells, regulatory T cells, B cells, and macrophages was objectively assessed with multispectral quantitative automated pathology imaging. Odds ratios for associations between physical activity and immune cell infiltration were estimated by logistic regression.

Results: A higher number of repetitions in the 30-second sit-to-stand test was associated with a lower density of T-helper 1 cells in the stromal compartment of the tumor, in the model adjusted for age and sex. When correcting for multiple testing the association was considered non-significant. No other significant association was seen for any of the physical tests or immune cell types in the multivariable logistic regression models.

Conclusions: No consistent evidence was found to support the hypothesis of an association between physical activity or fitness and increased immune cell tumor infiltration in colon cancer.

Trial registration: This study was registered at clinicaltrials.gov (ID: NCT03947840).

Abstract

Colon cancer surgery is associated with substantial postoperative decline in physical function, and preoperative physical status has been suggested to influence long-term recovery. However, evidence on how preoperative activity levels affect outcome up to one year after surgery remains limited.Our aim was to use objective data to evaluate how preoperative physical activity and status among colon cancer patients affects outcome six months and one year after colon cancer surgery.

Method

This prospective cohort study included 84 patients planned for elective colon cancer surgery. Preoperative physical function tests focusing on muscle strength and fitness were performed, and body DXA scan and accelerometer measurements were collected. Differences between pre- and postoperative measurements were analysed using linear mixed effect models. In the multivariable models, gender and adjuvant treatment were used as covariates.

Results

There was an increase in muscle mass despite a decrease in physical activity. Appendicular Skeletal Muscle Mass Index (ASMI) increased in both the uni- and multivariable model for both the 6- and 12-month follow-ups. Moderate to Vigorous Physical Activity (MVPA) decreased significantly at 12 months. Of the physical tests, an improvement in the 2-minute step test at 12 months was seen. Those patients who received adjuvant therapy had higher ASMI and MVPA than those who did not. These trends were the same in both groups.

Conclusion

Significant recovery in terms of greater muscle mass and better 2-min step test results was seen 6 and 12 months after colon cancer surgery despite a significant decline in physical activity. This knowledge is important when planning and designing studies on rehabilitation after surgery and prehabilitation.

Register: Clinicaltrials.gov, TRN. NCT03947840, Registration date: 30 January 2019.

Aim

To evaluate the association between objectively assessed preoperative physical activity and postoperative complication rate in colon cancer surgery.

Method

A prospective cohort study including 84 patients planned for elective colon cancer surgery. Preoperative physical function tests focusing on muscle strength and fitness were performed, and data from, body DXA scan, and accelerometer were collected. Logistic regression analyses were used to assess any association between preoperative physical status, MVPA (Moderate to Vigorous Physical Activity), or ASMI (Appendicular Skeletal Muscle Mass Index) with postoperative complication rate.

Results

Complications rated Clavien-Dindo ≥ 2 were seen in 15% of participants. High physical activity preoperatively was associated with a significant reduction in complication rate in the univariable analysis (OR 0.94, 95% CI 0.88-0.99, p=0.02). The mean daily MVPA in the group without complications was 40.2 minutes versus 9.2 minutes in the group with complications. In both univariable and multivariable analyses, there was a significantly lower complication rate associated with higher ASMI (OR 0.41, 95% CI 0.19-0.91, p=0.03).

Conclusion

This study shows that higher preoperative physical activity and muscle mass are associated with a lower postoperative complication rate. Physical activity recommendations should be given to all patients scheduled for elective colon cancer surgery.

Registry: Clinicaltrials.gov, TRN. NCT03947840, Registration date: 30 January 2019.