DNA methylation of exercise-responsive genes differs between trained and untrained men.

BACKGROUND: Physical activity is well known for its multiple health benefits and although the knowledge of the underlying molecular mechanisms is increasing, our understanding of the role of epigenetics in long-term training adaptation remains incomplete. In this intervention study, we included individuals with a history of > 15 years of regular endurance or resistance training compared to age-matched untrained controls performing endurance or resistance exercise. We examined skeletal muscle DNA methylation of genes involved in key adaptation processes, including myogenesis, gene regulation, angiogenesis and metabolism. RESULTS: A greater number of differentially methylated regions and differentially expressed genes were identified when comparing the endurance group with the control group than in the comparison between the strength group and the control group at baseline. Although the cellular composition of skeletal muscle samples was generally consistent across groups, variations were observed in the distribution of muscle fiber types. Slow-twitch fiber type genes MYH7 and MYL3 exhibited lower promoter methylation and elevated expression in endurance-trained athletes, while the same group showed higher methylation in transcription factors such as FOXO3, CREB5, and PGC-1α. The baseline DNA methylation state of those genes was associated with the transcriptional response to an acute bout of exercise. Acute exercise altered very few of the investigated CpG sites. CONCLUSIONS: Endurance- compared to resistance-trained athletes and untrained individuals demonstrated a different DNA methylation signature of selected skeletal muscle genes, which may influence transcriptional dynamics following a bout of acute exercise. Skeletal muscle fiber type distribution is associated with methylation of fiber type specific genes. Our results suggest that the baseline DNA methylation landscape in skeletal muscle influences the transcription of regulatory genes in response to an acute exercise bout.

Cancer-related fatigue: Towards a more targeted approach based on classification by biomarkers and psychological factors.

Cancer-related fatigue is a frequent, burdensome and often insufficiently treated symptom. A more targeted treatment of fatigue is urgently needed. Therefore, we examined biomarkers and clinical factors to identify fatigue subtypes with potentially different pathophysiologies. The study population comprised disease-free breast cancer survivors of a German population-based case-control study who were re-assessed on average 6 (FU1, n = 1871) and 11 years (FU2, n = 1295) after diagnosis. At FU1 and FU2, we assessed fatigue with the 20-item multidimensional Fatigue Assessment Questionnaire and further factors by structured telephone-interviews. Serum samples collected at FU1 were analyzed for IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-a, GM-CSF, IL-5, VEGF-A, SAA, CRP, VCAM-1, ICAM-1, leptin, adiponectin and resistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no history of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n = 195) on average had high levels of TNF-α, IL1-ß, IL-6, resistin, VEGF-A and GM-CSF, and showed high BMI and pain levels. Fatigue in CL1 manifested rather in physical dimensions. Contrarily, CL2 (n = 78) was characterized by high leptin level and had highest cognitive fatigue. CL3 (n = 318) did not show any prominent characteristics. Fatigued survivors with a history of depression (n = 214) had significantly higher physical, emotional and cognitive fatigue and showed significantly less amelioration of fatigue from FU1 to FU2 than survivors without depression. In conclusion, from the broad phenotype "cancer-related fatigue" we were able to delineate subgroups characterized by biomarkers or history of depression. Future investigations may take these subtypes into account, ultimately enabling a better targeted therapy of fatigue.

Post-diagnosis physical activity and sedentary behaviour and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose-response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%-60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.

Post-diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta-analysis on post-diagnosis adiposity measures (body mass index [BMI], waist circumference, waist-to-hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random-effects meta-analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta-analyses were possible for BMI and all-cause mortality, colorectal cancer-specific mortality, and cancer recurrence/disease-free survival. Non-linear meta-analysis indicated a reverse J-shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all-cause mortality; 95% and 26% for colorectal cancer-specific mortality; and 37% and 24% for cancer recurrence/disease-free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow-up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity-outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well-designed observational studies and interventional trials are needed to provide further clarification.

Post-diagnosis adiposity, physical activity, sedentary behaviour, dietary factors, supplement use and colorectal cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.

Post-diagnosis dietary factors, supplement use and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Longitudinal associations of diurnal rest-activity rhythms with fatigue, insomnia, and health-related quality of life in survivors of colorectal cancer up to 5 years post-treatment.

BACKGROUND: There is a growing population of survivors of colorectal cancer (CRC). Fatigue and insomnia are common symptoms after CRC, negatively influencing health-related quality of life (HRQoL). Besides increasing physical activity and decreasing sedentary behavior, the timing and patterns of physical activity and rest over the 24-h day (i.e. diurnal rest-activity rhythms) could also play a role in alleviating these symptoms and improving HRQoL. We investigated longitudinal associations of the diurnal rest-activity rhythm (RAR) with fatigue, insomnia, and HRQoL in survivors of CRC. METHODS: In a prospective cohort study among survivors of stage I-III CRC, 5 repeated measurements were performed from 6 weeks up to 5 years post-treatment. Parameters of RAR, including mesor, amplitude, acrophase, circadian quotient, dichotomy index, and 24-h autocorrelation coefficient, were assessed by a custom MATLAB program using data from tri-axial accelerometers worn on the upper thigh for 7 consecutive days. Fatigue, insomnia, and HRQoL were measured by validated questionnaires. Confounder-adjusted linear mixed models were applied to analyze longitudinal associations of RAR with fatigue, insomnia, and HRQoL from 6 weeks until 5 years post-treatment. Additionally, intra-individual and inter-individual associations over time were separated. RESULTS: Data were available from 289 survivors of CRC. All RAR parameters except for 24-h autocorrelation increased from 6 weeks to 6 months post-treatment, after which they remained relatively stable. A higher mesor, amplitude, circadian quotient, dichotomy index, and 24-h autocorrelation were statistically significantly associated with less fatigue and better HRQoL over time. A higher amplitude and circadian quotient were associated with lower insomnia. Most of these associations appeared driven by both within-person changes over time and between-person differences in RAR parameters. No significant associations were observed for acrophase. CONCLUSIONS: In the first five years after CRC treatment, adhering to a generally more active (mesor) and consistent (24-h autocorrelation) RAR, with a pronounced peak activity (amplitude) and a marked difference between daytime and nighttime activity (dichotomy index) was found to be associated with lower fatigue, lower insomnia, and a better HRQoL. Future intervention studies are needed to investigate if restoring RAR among survivors of CRC could help to alleviate symptoms of fatigue and insomnia while enhancing their HRQoL. TRIAL REGISTRATION: EnCoRe study NL6904 ( https://www.onderzoekmetmensen.nl/ ).

Patterns and influencing factors of exercise attendance of breast cancer patients during neoadjuvant chemotherapy.

BACKGROUND: Performing 2-3 exercise sessions/week may relieve therapy-related side effects of breast cancer patients (BRCA) and improve their quality of life. However, attendance to the exercise sessions is often impaired. Thus, we investigated patterns and possible influencing factors of attendance to an aerobic (AT) or resistance training (RT) intervention in BRCA during neoadjuvant chemotherapy. METHODS: BRCA (N = 122) were randomly allocated to supervised AT or RT twice weekly during neoadjuvant chemotherapy (18 ± 4 weeks). Attendance was calculated individually and group-wise per training week as the percentage of the performed sessions out of the prescribed sessions. Possible influencing factors were investigated using multiple regression analyses. RESULTS: Mean individual attendance was 44.1% ± 29.3% with no significant differences between the groups. Group-wise attendance was highest in the first 6 weeks of training with ≥ 60% for AT and ≥ 50% for RT, but decreased over the course of the intervention accompanying chemotherapy. Significantly higher attendance was associated with not having vs. having nausea (ß = - 14.57; p = 0.007) and not having vs. having pain (ß = - 12.07; p = 0.12), whereas fatigue did not show any association (ß = - 0.006; p = 0.96). Having been randomized into a preferred intervention group (48.8%) showed no association with attendance. Yet, patients' rating of the exercise intervention as "good"/ "very good" (58.7%) was significantly associated with higher attendance (p = 0.01). CONCLUSION: For both exercise interventions, group-wise attendance/training week decreased during chemotherapy despite good intervention ratings. While some patients never started, others trained almost constantly twice weekly. The study revealed that patients who are nauseous or experience pain may need more support to attend more exercise sessions. Trial Registration Clinicaltrials.gov: NCT02999074 from May 6, 2016.

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/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 >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.

Changes in physical activity and sedentary behavior during the first COVID-19 pandemic- restrictions in Germany: a nationwide survey : Running head: physical activity during the COVID-19 restrictions.

BACKGROUND: The COVID-19 pandemic restrictions posed challenges to maintaining healthy lifestyles and physical well-being. During the first mobility restrictions from March to mid-July 2020, the German population was advised to stay home, except for work, exercise, and essential shopping. Our objective was to comprehensively assess the impact of these restrictions on changes in physical activity and sedentary behavior to identify the most affected groups. METHODS: Between April 30, 2020, and May 12, 2020, we distributed a COVID-19-specific questionnaire to participants of the German National Cohort (NAKO). This questionnaire gathered information about participants' physical activity and sedentary behavior currently compared to the time before the restrictions. We integrated this new data with existing information on anxiety, depressive symptoms, and physical activity. The analyses focused on sociodemographic factors, social relationships, physical health, and working conditions. RESULTS: Out of 152,421 respondents, a significant proportion reported altered physical activity and sedentary behavioral patterns due to COVID-19 restrictions. Over a third of the participants initially meeting the WHO's physical activity recommendation could no longer meet the guidelines during the restrictions. Participants reported substantial declines in sports activities (mean change (M) = -0.38; 95% CI: -.390; -.378; range from -2 to + 2) and reduced active transportation (M = -0.12; 95% CI: -.126; -.117). However, they also increased recreational physical activities (M = 0.12; 95% CI: .117; .126) while engaging in more sedentary behavior (M = 0.24; 95% CI: .240; .247) compared to pre-restriction levels. Multivariable linear and log-binomial regression models indicated that younger adults were more affected by the restrictions than older adults. The shift to remote work, self-rated health, and depressive symptoms were the factors most strongly associated with changes in all physical activity domains, including sedentary behavior, and the likelihood to continue following the physical activity guidelines. CONCLUSIONS: Mobility patterns shifted towards inactivity or low-intensity activities during the nationwide restrictions in the spring of 2020, potentially leading to considerable and lasting health risks.

Longitudinal associations of bioelectrical phase angle and fatigue in breast cancer patients.

Cancer-related fatigue is commonly treated in an undifferentiated manner, because its pathophysiology is still not well understood. Therefore, we investigated if bioelectrical phase angle (PhA), a non-invasive marker of cell integrity, could help to single out specific fatigue subtypes. In a randomized controlled strength training intervention trial, PhA was measured by bioelectrical impedance analysis in 158 breast cancer patients. Fatigue was assessed with the multidimensional 20-item Fatigue Assessment Questionnaire. Multiple regression analyses considering changes in PhA and fatigue from baseline to post-intervention and ANCOVA models investigating the strength training effect on PhA were conducted. Further, explorative mediation and moderation analyses were performed. Decrease (=worsening) in PhA was significantly associated with increase in physical (P = .010) and emotional (P = .019) fatigue. These associations were markedly stronger in patients with normal BMI (interaction P = .059 and .097) and with low pre-diagnosis exercise level (interaction P = .058 and .19). Among patients with normal BMI strength training was associated with an increase in PhA (ANCOVA P = .059), but not among overweight/obese patients (interaction P = .035). Chemotherapy was a major determinant for low PhA, but PhA did not mediate the effect of chemotherapy on fatigue. In conclusion, PhA has a significant inverse association with physical and emotional fatigue. This association is moderated by BMI and previous exercise. Significant relationships of PhA were also observed with chemotherapy and strength training. Thus, PhA might be a marker that could help in the classification of subtypes of fatigue with different pathophysiology, which may require specifically tailored treatment. Further research on this is warranted.

Long-term effects of exercise interventions on physical activity in breast cancer patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Benefits of exercise interventions for cancer patients are well established. This systematic review aimed to investigate the sustainability of exercise interventions with respect to physical activity behaviour of breast cancer patients in the longer term. METHODS: The databases Pubmed, Cochrane, Embase, and Web of Science were systematically searched for randomized controlled trials (RCTs) investigating aerobic exercise, resistance exercise, or combined exercise interventions in breast cancer patients and assessing physical activity at least 2 months after the intervention. Random-effect models were used to calculate standardized mean differences (SMD). RESULTS: A total of 27 RCTs with 4120 participants were included in the review, of which 11 RCTs with 1545 participants had appropriate data for the meta-analyses. Physical activity was mainly self-reported, and most exercise interventions were supervised. Exercise interventions tended to show a moderate significant effect up to 6 months for moderate to vigorous physical activity (SMD [95% CI] = 0.39 [0.07, 0.70]) and small, non-significant effects on total physical activity at 6 months (SMD [95% CI] = 0.14 [- 0.00, 0.28]) and up to 60 months after the intervention (SMD = 0.29 [-0.31, 0.90]). Differences between intervention characteristics, such as supervised versus unsupervised, were inconclusive due to the small number of RCTs. CONCLUSIONS: The physical activity behaviour in breast cancer patients remained improved for several months beyond the end of exercise interventions, but effects were small to moderate and diminished over time. Future studies should clarify how to maintain a healthy level of physical activity after completion of an exercise intervention.

Psycho-oncologists' knowledge of cancer-related fatigue and the targets for improving education and training: results from a cross-sectional survey study.

PURPOSE: To explore psycho-oncologists' knowledge of cancer-related fatigue and their self-efficacy to intervene for fatigue. We further aimed to examine the role of fatigue in psycho-oncological training and derive specific suggestions for improvements. METHODS: For this cross-sectional survey study, psycho-oncologists working in Germany were systematically recruited via an address directory or invited by training institutes or colleagues. The online survey encompassed questions on knowledge of fatigue guidelines and interventions, self-efficacy, counseling, and fatigue in professional training. Data were analyzed descriptively and using Mann-Whitney U tests. A logistic regression analysis was performed to identify variables linked to fatigue guideline knowledge. RESULTS: Seventy two percent of the 144 surveyed psycho-oncologists stated not knowing any fatigue-specific guidelines. Those unaware of guidelines reported a lower self-efficacy to intervene for fatigue. However, despite low knowledge of the guidelines, more than 80% of the participants felt well informed about fatigue and reported high self-efficacy. Most participants were aware of the empirical evidence for psychotherapeutic interventions (95%); everyday physical activity, e.g., taking a walk (98%); yoga (82%); and mindfulness-based interventions (82%). Knowledge gaps existed concerning the evidence of resistance/endurance training for treating fatigue. Knowing that resistance/endurance training is an effective treatment was related to an increased frequency to recommend it to patients. Suggestions to improve training for psycho-oncologists included raising awareness earlier in the career path and offering multidisciplinary trainings for fatigue. CONCLUSION: To improve fatigue-related guideline knowledge among psycho-oncologists and enhance implementation into clinical practice multidisciplinary trainings are needed. Psycho-oncologists should play an important role in fatigue management. TRIAL REGISTRATION: Clinicaltrials.gov , identifier: NCT04921644. Registered in June 2021.

PERSPECTIVEs on supervised exercise programs in people with metastatic breast cancer- a qualitative study in four European countries.

PURPOSE: Supervised exercise is a potentially promising supportive care intervention for people with metastatic breast cancer (MBC), but research on the patients' perspective is limited. The aim of the current focus group study was to gain an in-depth understanding of MBC patients' perceived barriers, facilitators, and preferences for supervised exercise programs. METHODS: Eleven online focus groups with, in total, 44 MBC patients were conducted in four European countries (Germany, Poland, Spain, Sweden). Main topics of the semi-structured discussions covered attitudes towards participation in supervised exercise programs, perceived facilitators, experienced barriers, and exercise preferences. Interviews were transcribed verbatim, translated into English, and coded based on a preliminary coding framework, supplemented by themes emerging during the sessions. The codes were subsequently examined for interrelations and re-organized into overarching clusters. RESULTS: Participants had positive attitudes towards exercise, but experienced physical limitations and insecurities that inhibited their participation. They expressed a strong desire for exercise tailored to their needs, and supervision by an exercise professional. Participants also highlighted the social nature of group training as an important facilitator. They had no clear preference for exercise type, but rather favored a mixture of different activities. Flexible training modules were considered helpful to increase exercise program adherence. CONCLUSIONS: MBC patients were generally interested in supervised exercise programs. They preferred group exercise that facilitates social interaction, but also expressed a need for individualized exercise programs. This suggests the relevance to develop flexible exercise programs that are adjusted to the individual's needs, abilities, and preferences.

Perspectives of patients with metastatic breast cancer on physical exercise programs: results from a survey in five European countries.

BACKGROUND: To successfully implement exercise programs for patients with metastatic breast cancer (MBC), services and patient education should consider patients' knowledge, preferences, values, and goals. Hence, gaining insight into their perspectives on exercise and exercise programming is important. METHOD: In this cross-sectional survey, we recruited patients with MBC from the Netherlands, Germany, Poland, Spain, and Sweden. We collected data on patients' knowledge and skills about exercise and outcome expectations. We identified barriers to and facilitators of participation in exercise programs, and patients' preferences for program content and modes of exercise delivery. RESULTS: A total of 420 patients participated in the survey. Respondents were, on average, 56.5 years old (SD 10.8) and 70% had bone metastases. Sixty-eight percent reported sufficient skills to engage in aerobic exercise, but only 35% did so for resistance exercise. Respondents expected exercise to have multiple physical benefits, but a few patients expected exercise to worsen their pain (5%). Not having access to an exercise program for cancer patients (27%), feeling too tired (23%), and/or weak (23%) were the most often reported barriers. Facilitators for exercising regularly were previous positive physical (72%) and emotional (68%) experiences with exercising, and receiving personalized advice from a physiotherapist or sport/fitness instructor (62%). Patients were most interested in walking and preferred exercising at a public gym, although there were differences by country. Fifty-seven percent did not know whether their insurance company reimburses exercise programs and only 9% would be willing to pay more than €50 per month to participate. CONCLUSION: A large percentage of patients with MBC lack the skills to engage in regular exercise as recommended by exercise guidelines for people with cancer. Patients may benefit from personalized advice and appropriate training facilities to overcome barriers. When implementing exercise interventions, attention should be given to reimbursement and the relatively low willingness-to-pay.

Determinants of physical activity during cancer treatment: a longitudinal exploration of psycho-cognitive variables and physician counseling.

Individuals with cancer are recommended to engage in regular physical activity (PA) even during cancer therapy. The aim of this study was to explore how patient-reported physician PA counseling influences their PA intention and behavior in addition to psycho-cognitive determinants derived from the theory of planned behavior (TPB). A longitudinal study during cancer treatment was conducted among N = 115 patients with breast, prostate, or colorectal cancer (Mage = 58.0, SD = 11.5; 55.7% female). The median time since diagnosis was 2 months, and 19.1% were diagnosed with metastases. Participants provided information on PA counseling by their physicians and on psycho-cognitive variables of the TPB at three measurement points. Additionally, they wore accelerometers for seven days at baseline and three months later. Nearly half of participants (48%) reported basic PA counseling and 30% reported in-depth PA counseling. Patients in poorer health and with lower education reported significantly less in-depth counseling. In addition to patient self-efficacy in performing PA, only in-depth physician PA counseling, but not basic physician counseling, predicted intention for PA four weeks later. Patients' PA three months after baseline was predicted by patients' PA at baseline and their intention for PA. Overall, the PA level at baseline was identified as the most important predictor of PA three months later. Nevertheless, physicians seem to have the ability to increase their cancer patients' intention for PA by in-depth counseling.

Late effects, long-term problems and unmet needs of cancer survivors.

Great efforts are being made in cancer treatment, with impressive improvement in survival. The situation concerning research and care for long-term problems and late effects in the growing population of cancer survivors, however, is unsatisfactory. Therefore, in the FiX survey 1348 disease-free survivors about 4 years after diagnosis of different cancer types were asked to rate existing burdens and support received for them along a list of 36 potential problems. Health-related quality of life (HRQoL) was assessed with the EORTC QLQ-C30. Determinants of burdens were explored using logistic regression analysis. While cancer survivors' global HRQoL, physical and role function ratings were comparable or better than age- and sex-matched reference values of the general population, emotional and cognitive function was worse, especially among women (P < .01). Most frequently reported problems with at least moderate burden were loss of physical performance (36.3%), fatigue (35.1%), sexual problems (34.7%), sleep problems (34.1%), arthralgia (33.8%), anxiety (28.0%), neuropathy (25.6%), memory problems (23.0%) and concentration problems (21.9%). Burdened survivors often rated received support as poor, especially regarding support for problems that physicians might consider medically nonthreatening, or for which no effective pharmacologic or medical treatment is known. Determinants for burden included higher age, female gender, having ever received chemotherapy and overweight/obesity. In conclusion, a significant number of cancer survivors suffer from long-term or late effects and have unmet care needs. Awareness of health care professionals should be increased for these issues. The results of our study can contribute to the development of targeted survivorship plans.

Nutrition Intake and Nutrition Status of Pancreatic Cancer Patients: Cross-Sectional and Longitudinal Analysis of a Randomized Controlled Exercise Intervention Study.

Pancreatic cancer patients often present with an inadequate nutritional intake. At the same time, there are no standardized recommendations for nutrition intake during and after cancer treatment. In a prospective analysis of a randomized controlled trial analyzing the effects of a 6-month resistance training in pancreatic cancer patients, we assessed the nutritional intake and the impact of a 6-month supervised resistance training or home-based resistance training vs. usual care control on the nutritional intake of the patients. Nutritional intake was assessed by 24-h recall before and after the 6-month resistance training period. At baseline low protein intake (<1 g/kg body weight) was found in 33.9% of the 59 patients and low energy intake (<25 kcal/kg body weight) was found in 39.0% of the patients. In all, 35.6% of the patients were classified with a risk of malnutrition (NRS ≥ 3). In the total of 46 patients who finished the 6-month intervention period, there was no difference in nutritional intake over time between resistance training and usual care control. In conclusion, it appears that the majority of our study population had an adequate protein and energy intake. A resistance training seems to have no influence on the nutritional intake of the patients.

Cancer-related fatigue: Identification of hallmarks to enable refined treatment approaches.

OBJECTIVE: Recommendations for fatigue management are commonly given in an undifferentiated manner without further evaluation of patient's specific symptomatology. Thus, we aimed to identify hallmarks of potential fatigue subgroups which might guide more refined treatment. METHODS: The FiX study assessed fatigue with the EORTC QLQ-FA12 in patients around 2 years after cancer diagnosis (T0) including 15 different entities. After 2 years, a follow-up survey (T1) was conducted. The analyses comprised all patients with prevalent fatigue at T0 (N = 1023). Hierarchical cluster analysis was performed using the Ward method and including the dichotomized factors emotional distress, pain, insomnia, and obesity. Emotional distress, that is, depressive symptoms and anxiety, was assessed by the PHQ-4. Pain and insomnia were based on the according symptom scores of the EORTC QLQ-C30. Analysis of covariance was conducted to investigate the association of the fatigue clusters at T0 with subsequent fatigue at T1. RESULTS: Four hierarchical clusters were identified. The first cluster comprised patients with moderate-to-severe distress. The remaining fatigue cases were differentiated by obesity and then by pain. Fatigue cases without any of these three symptoms formed the last cluster. Physical, emotional and cognitive fatigue were highest in the distress cluster. Additionally, this cluster was associated with higher physical, emotional and cognitive fatigue at T1 compared to the other clusters. CONCLUSIONS: Fatigue in conjunction with emotional distress had worse impact, persisted longer, and may require other treatment approaches than fatigue in patients without emotional distress. Obesity and pain may be further distinguishing hallmarks for refined fatigue management.

The cancer patients' perspective on feasibility of using a fatigue diary and the benefits on self-management: results from a longitudinal study.

PURPOSE: To evaluate the patients' perspective on feasibility of using a fatigue diary and its benefits on self-management. METHODS: This longitudinal study enrolled 50 cancer patients in routine care. Following baseline (t0) assessment, patients were asked to complete a 7-day fatigue diary and subsequently obtained written diary evaluation. Feasibility, benefits, and fatigue-related attitudes were assessed via self-report 1 (t1) and 4 months (t2) after distributing the diary. Data were analyzed descriptively and using Wilcoxon signed-rank tests. RESULTS: Most patients (94%) completed the diary for 7 days and rated feasibility as high. After diary completion and receiving the evaluation, fewer patients felt helpless in the face of fatigue (t1: 21% vs. t0: 53%). Additionally, more patients addressed fatigue with their general practitioner (t2: 49% vs. t0: 36%) and pro-actively searched for information and help (t2: 59% vs. t0: 38%). The diary enabled a majority of patients to be aware of their fatigue patterns, to plan daily routines accordingly and to take adequate actions against fatigue. CONCLUSION: The study showed that symptom monitoring via a fatigue diary was considered feasible and enhanced self-management in cancer patients. Thus, fatigue diaries might be a useful measure contributing to an improved fatigue management. The results reinforce guideline recommendations for routine application of fatigue diaries in clinical care. Healthcare professionals should encourage patients to fatigue diary use and provide individually tailored counseling based on diary entries.