Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study

Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI &gt;28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI &gt;28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.</p

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m 2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m 2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m 2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects

Comparing saliva and urine samples for measuring breastmilk intake with the deuterium oxide dose-to-mother technique among children 2-4 months old

Saliva and urine are the two main body fluids sampled when breastmilk intake is measured with the deuterium oxide dose-to-mother technique. However, these two body fluids may generate different estimates of breastmilk intake due to differences in isotope enrichment. Therefore, we aimed to assess how the estimated amount of breastmilk intake differs when based on saliva and urine samples and to explore whether the total energy expenditure of the mothers is related to breastmilk output. We used a convenience sample of 13 pairs of mothers and babies aged 2 to 4 months, who were exclusively breastfed and apparently healthy. To assess breastmilk intake, we administered doubly labelled water to the mothers, and collected saliva samples from them, while simultaneously collecting both saliva and urine from their babies over a 14-day period. IRMS was used to analyze the samples for deuterium and oxygen-18 enrichments. Mean breastmilk intake based on saliva samples was significantly higher than that based on urine samples (854.5g/day vs. 812.8g/day, p=0.029). This can be attributed to slightly higher isotope enrichments in saliva and to a poorer model fit for urine samples as indicated by a higher square root of the mean square error (14.6 vs. 10.4 mg/kg, p=0.001). Maternal energy expenditure was not correlated with breastmilk output. Our study suggests that saliva sampling generates slightly higher estimates of breastmilk intake and is more precise as compared to urine and that maternal energy expenditure does not influence breastmilk output</p

Comparing saliva and urine samples for measuring breastmilk intake with the deuterium oxide dose-to-mother technique among children 2-4 months old

Saliva and urine are the two main body fluids sampled when breastmilk intake is measured with the deuterium oxide dose-to-mother technique. However, these two body fluids may generate different estimates of breastmilk intake due to differences in isotope enrichment. Therefore, we aimed to assess how the estimated amount of breastmilk intake differs when based on saliva and urine samples and to explore whether the total energy expenditure of the mothers is related to breastmilk output. We used a convenience sample of 13 pairs of mothers and babies aged 2 to 4 months, who were exclusively breastfed and apparently healthy. To assess breastmilk intake, we administered doubly labelled water to the mothers, and collected saliva samples from them, while simultaneously collecting both saliva and urine from their babies over a 14-day period. IRMS was used to analyze the samples for deuterium and oxygen-18 enrichments. Mean breastmilk intake based on saliva samples was significantly higher than that based on urine samples (854.5g/day vs. 812.8g/day, p=0.029). This can be attributed to slightly higher isotope enrichments in saliva and to a poorer model fit for urine samples as indicated by a higher square root of the mean square error (14.6 vs. 10.4 mg/kg, p=0.001). Maternal energy expenditure was not correlated with breastmilk output. Our study suggests that saliva sampling generates slightly higher estimates of breastmilk intake and is more precise as compared to urine and that maternal energy expenditure does not influence breastmilk output.</p

Cross-Sectional Associations between Dietary Daily Nicotinamide Intake and Patient-Reported Outcomes in Colorectal Cancer Survivors, 2 to 10 Years Post-Diagnosis

Supplementation with nicotinamide adenine dinucleotide (NAD+) precursors including dietary nicotinamide has been found to boost tissue NAD+ levels and ameliorate oxidative stress-induced damage that contributes to aging and aging-related diseases. The association between dietary NAD+ precursors and patient-reported health-related outcomes in cancer survivors has not been investigated. This study aimed to determine associations of dietary nicotinamide intake with different patient-reported outcomes in colorectal cancer survivors, 2 to 10 years post-diagnosis. A total of 145 eligible participants were recruited into this cross-sectional study. Dietary nicotinamide intake level was calculated based on data from 7-day food diaries. Fatigue was assessed with the Checklist Individual Strength (CIS), which is a subscale of the cancer-specific European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC), and anxiety and depression were assessed with Hospital Anxiety and Depression Scale (HADS). Oxidative stress marker serum protein carbonyl contents and serum NAD+ levels were measured. A hierarchical linear regression model with confounder adjustment was performed to analyze the association of nicotinamide intake, serum protein carbonyl contents, and NAD+ levels with patient-reported outcomes. The median values of daily nicotinamide intake for male and female participants were 19.1 and 14.4 mg, respectively. Daily dietary nicotinamide intake was associated with a lower level of fatigue (β: −14.85 (−28.14, −1.56)) and a lower level of anxiety and depression (β: −4.69 (−8.55, −0.83)). Subgroup analyses by sex showed that a beneficial association between nicotinamide intake and patient-reported outcomes was mainly found in men. To conclude, our findings suggested that higher dietary NAD+ precursor nicotinamide intake was cross-sectionally associated with less patient-reported outcomes in CRC survivors

Exercise and the gut microbiome : implications for supportive care in cancer

Purpose: Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population. Methods: A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors. Results: Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists. Conclusions: Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature

Longitudinal associations of fast foods, red and processed meat, alcohol and sugar-sweetened drinks with quality of life and symptoms in colorectal cancer survivors up to 24 months post-treatment

Unhealthy dietary habits can contribute to the development of colorectal cancer (CRC). Such habits may also be associated with post-treatment symptoms experienced by CRC survivors. Therefore, we aimed to assess longitudinal associations of post-treatment unhealthy dietary habits, i.e. intake of ultra-processed foods (UPF), red and processed meat, alcohol and sugar-sweetened drinks, with health-related quality of life (HRQoL), fatigue and chemotherapy-induced peripheral neuropathy (CIPN) in CRC survivors from 6 weeks up to 24 months post-treatment. In a prospective cohort among stage I-III CRC survivors (n 396), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Dietary intake was measured by 7-d dietary records to quantify consumption of UPF, red and processed meat, alcohol and sugar-sweetened drinks. HRQoL, fatigue and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyse longitudinal associations from 6 weeks until 24 months post-treatment. We applied a post hoc time-lag analysis for alcohol to explore the directionality. Results showed that higher post-treatment intake of UPF and sugar-sweetened drinks was longitudinally associated with worsened HRQoL and more fatigue, while higher intake of UPF and processed meat was associated with increased CIPN symptoms. In contrast, post-treatment increases in alcohol intake were longitudinally associated with better HRQoL and less fatigue; however, time-lag analysis attenuated these associations. In conclusion, unhealthy dietary habits are longitudinally associated with lower HRQoL and more symptoms, except for alcohol. Results from time-lag analysis suggest no biological effect of alcohol; hence, the longitudinal association for alcohol should be interpreted with caution

Longitudinal Associations of Adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Lifestyle Recommendations with Quality of Life and Symptoms in Colorectal Cancer Survivors up to 24 Months Post-Treatment

Post-treatment adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations were associated with health-related quality of life (HRQoL), fatigue, and chemotherapy-induced peripheral neuropathy (CIPN) in colorectal cancer (CRC) survivors. In a prospective cohort among CRC survivors (n = 459), repeated home-visits were performed at 6 weeks, 6, 12, and 24 months post-treatment. Dietary intake, body composition, sedentary behaviour, and physical activity were assessed to construct a lifestyle score based on adherence to seven 2018 WCRF/AICR recommendations. Longitudinal associations of the lifestyle score with HRQoL, fatigue, and CIPN were analysed by confounder-adjusted linear mixed models. A higher lifestyle score was associated with better physical functioning and less activity-related fatigue, but not with CIPN. Adjustment for physical activity substantially attenuated observed associations, indicating its importance in the lifestyle score with regards to HRQoL. In contrast, adjustment for body composition and alcohol inflated observed associations, indicating that both recommendations had a counteractive influence within the lifestyle score. Our findings suggest that CRC survivors benefit from an overall adherence to the WCRF/AICR lifestyle recommendations in terms of HRQoL and fatigue, but not CIPN. Specific recommendations have a varying influence on these associations, complicating the interpretation and requiring further study

Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Background: Fatigue is often reported by colorectal cancer survivors and largely impacts their quality of life. Inflammation has been linked to fatigue mainly in patients with breast cancer. Therefore, we investigated how inflammation is longitudinally associated with fatigue in colorectal cancer survivors, up to 2 years posttreatment. Methods: A total of 257 patients from the ongoing Energy for life after ColoRectal cancer cohort study were included in the analysis. Plasma levels of IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and fatigue were measured at 6 weeks, 6, 12, and 24 months posttreatment. Fatigue was measured through the validated Checklist Individual Strength (CIS; total, 20-140), consisting of four subscales - subjective fatigue (8-56), motivation (4-28), physical activity (3-21), and concentration (5-35), and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 fatigue subscale (0-100). Linear mixed-models were used to assess the confounder-adjusted longitudinal associations between inflammatory markers and overall fatigue along with the subscales. Results: Mean levels of CIS fatigue decreased from 62.9 at 6 weeks to 53.0 at 24 months. In general, levels of inflammatory markers also decreased over time. No statistically significant longitudinal associations were found between IL6, IL8, IL10, TNFα, and fatigue. Higher levels of hsCRP were associated with more CIS fatigue (β per SD 3.21, 95% confidence interval (CI), 1.42-5.01) and EORTC fatigue (β 2.41, 95% CI, 0.72-4.10). Conclusions: Increased levels of hsCRP are longitudinally associated with more posttreatment fatigue in colorectal cancer survivors. Impact: These findings suggest that low-grade inflammation may play a role in fatigue reported by colorectal cancer survivors up to 2 years posttreatment