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/ ).

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.

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.

Costs associated with insufficient physical activity in Germany: cross-sectional results from the baseline examination of the German national cohort (NAKO).

BACKGROUND: Insufficient physical activity (PA) is a leading risk factor for non-communicable diseases posing a significant economic burden to healthcare systems and societies. The study aimed to examine the differences in healthcare and indirect costs between sufficient and insufficient PA and the cost differences between PA intensity groups. METHODS: The cross-sectional analysis was based on data from 157,648 participants in the baseline examination of the German National Cohort (NAKO) study. Healthcare and indirect costs were calculated based on self-reported information on health-related resource use and productivity losses. PA in the domains leisure, transport, and work was assessed by the Global Physical Activity Questionnaire and categorized into sufficient/insufficient and intensity levels (very low/low/medium/high) based on PA recommendations of the World Health Organization. Two-part models adjusted for relevant covariates were used to estimate mean costs for PA groups. RESULTS AND CONCLUSION: Insufficiently active people had higher average annual healthcare costs (Δ €188, 95% CI [64, 311]) and healthcare plus indirect costs (Δ €482, 95% CI [262, 702]) compared to sufficiently active people. The difference was especially evident in the population aged 60 + years and when considering only leisure PA. An inverse association was observed between leisure PA and costs, whereas a direct association was found between PA at work and costs. Adjusting for the number of comorbidities reduced the differences between activity groups, but the trend persisted. The association between PA and costs differed in direction between PA domains. Future research may provide further insight into the temporal relationship between PA and costs.

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.

Large-scale assessment of physical activity in a population using high-resolution hip-worn accelerometry: the German National Cohort (NAKO).

Large population-based cohort studies utilizing device-based measures of physical activity are crucial to close important research gaps regarding the potential protective effects of physical activity on chronic diseases. The present study details the quality control processes and the derivation of physical activity metrics from 100 Hz accelerometer data collected in the German National Cohort (NAKO). During the 2014 to 2019 baseline assessment, a subsample of NAKO participants wore a triaxial ActiGraph accelerometer on their right hip for seven consecutive days. Auto-calibration, signal feature calculations including Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD), identification of non-wear time, and imputation, were conducted using the R package GGIR version 2.10-3. A total of 73,334 participants contributed data for accelerometry analysis, of whom 63,236 provided valid data. The average ENMO was 11.7 ± 3.7 mg (milli gravitational acceleration) and the average MAD was 19.9 ± 6.1 mg. Notably, acceleration summary metrics were higher in men than women and diminished with increasing age. Work generated in the present study will facilitate harmonized analysis, reproducibility, and utilization of NAKO accelerometry data. The NAKO accelerometry dataset represents a valuable asset for physical activity research and will be accessible through a specified application process.

Post-traumatic growth in cancer survivors: What is its extent and what are important determinants? / Crecimiento postraumático en sobrevivientes de cáncer: ¿cuál es su alcance y cuáles son sus determinantes importantes?

Background/Objective: The aim was to investigate the extent and longitudinal determinants of post-traumatic growth (PTG) in cancer survivors. Methods: A sample of 1316 cancer survivors with various cancer types was examined using the EORTC QLQ-FA12 to assess fatigue, the EORTC QLQ-C30 pain items to assess pain and the Patient Health Questionnaire (PHQ-4) to assess emotional distress two years after diagnosis (t0). Additionally, patients rated how well they felt informed about fatigue at t0. PTG was assessed with the 21-item PTG-Inventory four years after diagnosis (t1) comprising the five subdimensions appreciation of life, relation to others, personal strengths, new possibilities and spiritual change. Results: Regarding the extent of PTG, most positive developments were experienced in the PTG subdimension appreciation of life whereas the subdimension spiritual change was the least pronounced domain. Fatigue, pain and emotional distress were longitudinal but non-linear predictors of long-term PTG. Additionally, poor informedness about fatigue was associated with less PTG. Conclusions: PTG can be perceived even years after a traumatic cancer event and is longitudinally associated with common cancer side effects like fatigue, emotional distress and pain. Further research into the role of individuals' informedness contributing to PTG is needed.(AU)

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.

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.

Cancer-related fatigue: Quality, credibility, usability, and readability of information on websites of health care institutions in Germany.

OBJECTIVES: This study aimed to portray available information on cancer-related fatigue on German health care institution websites considering the idea of patient empowerment. METHODS: Based on website quality criteria, we developed a website-rating tool comprising 18 items. Descriptive analyses, a KruskalWallis test, and corresponding post hoc tests comparing rating sum scores between institution groups were performed. RESULTS: Websites of 283 systematically compiled health care institutions were included in the rating. Cancer-related fatigue was introduced on 21.9% and detailed information was provided on 27.9% of the websites. Information material was offered on 9.2% of the websites, while fatigue treatment offers were presented on 21.6% of the websites. The rating sum scores differed between institution groups (p < 0.001), with Comprehensive Cancer Centers scoring significantly higher than the others. CONCLUSION: The rating revealed an overall sparse provision of information, with fatigue being addressed on less than half of the websites. PRACTICE IMPLICATIONS: For patients who have access to at least one introduction about fatigue, institutions need to extend their websites. Patients could further be referred to external institutions or information booklets. The naming of contact persons may help linking patients to providers.

Patient-physician communication about cancer-related fatigue: a survey of patient-perceived barriers.

PURPOSE: Cancer-related fatigue is a subjective, distressing, and common sequela of cancer which is often disregarded and underdiagnosed. Fatigue is assessed by self-report requiring communication between patient and physician. In this study, we investigated the patients' perspective on the patient-physician communication about fatigue. METHODS: On average five months after diagnosis 1179 cancer patients, recruited in Germany, completed a survey as part of the LIFT project. The survey included questions on sociodemographic data, fatigue, depression, fatigue management, patient-physician communication, and communication barriers. Data were analyzed descriptively and using logistic regression analyses. RESULTS: Half of the participants reported that their physician had never asked them whether they felt exhausted. Patients undergoing chemo-, radio-, or immunotherapy were more likely to be asked about fatigue, while older age and major depression decreased the likelihood. Sixty-four percent of the patients felt impeded by communication barriers. Common barriers were not knowing who to turn to for fatigue (39%), time constraints (31%), and the fear of being perceived as weak (22%). Almost half of the participants indicated that their physicians were not appreciative and did not deal adequately with fatigue-related questions. CONCLUSION: This study revealed gaps in the patient-physician communication regarding cancer-related fatigue. Contrary to guideline recommendations a minority of physicians addressed fatigue. On the other hand, cancer patients felt reluctant to bring up this topic due to structural barriers and fears. Physicians should routinely address fatigue and adopt a communication style which encourages patients to likewise state their symptoms and raise their questions. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04921644. Registered in June 2021.

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.

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

PURPOSE: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

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.

Posttraumatic growth and health-related quality of life in cancer survivors: Does fatigue moderate the link?

Interest in post-traumatic growth (PTG) as a predictor of health-related quality of life (HRQoL) is currently gaining attention. However, current evidence is still inconclusive on the nature of this relationship. The first objective of this study was to investigate the relationship between PTG and global HRQoL among cancer survivors. We further investigated the moderating role of fatigue in the association between PTG and global HRQoL. In the FiX study (Fatigue in Germany - Examination of prevalence, severity, and state of screening and treatment) cancer-related fatigue (EORTC QLQ-FA12), PTG inventory and global HRQoL (EORTC QLQ-C30) were assessed four years after cancer diagnosis in 1316 cancer-free survivors (mean age = 67.28, SD = 11.05, 51.4% female). Multiple linear regression analysis and moderation analysis were performed. The results showed that PTG had a convex quadratic relationship with global HRQoL (p < 0.001). Contrary to our hypothesis, fatigue did not moderate the relationship between PTG (linear and quadratic terms) and global HRQoL, neither when considering the overall PTG score nor for any PTG subdimension. In conclusion, PTG has a convex quadratic relationship with long-term global HRQoL that was not modified by persisting fatigue. Future statistical models investigating PTG and global HRQoL should take this non-linear relationship into account. Aiming to increase PTG might contribute to, but is likely not sufficient for high levels of global HRQoL in cancer survivors in the long run.

Maintenance of Aerobic or Resistance Training After an Exercise Intervention Among Breast Cancer Patients After Neoadjuvant Chemotherapy.

BACKGROUND: Exercise interventions have been shown to be beneficial for cancer patients regarding various treatment-related side effects and quality of life. For sustainable effects, patients should continue the training. Therefore, we investigated the maintenance of an exercise training in breast cancer patients, reasons for (dis)continuation, and explored possible influencing factors. METHODS: The investigation is based on a 3-arm randomized intervention trial comparing aerobic and resistance training (19 [4]) during or after neoadjuvant chemotherapy among breast cancer patients. About 2 years after breast surgery, 68 patients (age 52 [11] y) provided information about training continuation, self-reported reasons of (dis)continuation, sociodemographics, employment status, age, and body mass index. Training continuation was investigated with Kaplan-Meier analyses. RESULTS: The intervention was rated as good or very good by 88.1% of participants. Nevertheless, 52.9% discontinued the training directly, but half of them changed to different types of exercise. Reasons for discontinuation included lack of time and long travel distance to the training facility. The median continuation was 19.0 months (Q1, Q3: 5.5, 36.0) with no statistically significant difference between the intervention groups. Younger, better educated, partnered patients tended toward longer training continuation. CONCLUSIONS: The majority of patients continued exercising after the end of intervention. However, a nonnegligible number discontinued training immediately or after few months. Practical, social, and financial support for a transition to an adequate training that is affordable and feasible in the patient's daily life might foster training maintenance. Especially patients who are less educated, elderly, or living alone may need more support to continue exercising.

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.

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.

Protocol of the IntenSify-Trial: An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy.

Expression of CYP3A5 protein is a basal and acquired resistance mechanism of pancreatic ductal adenocarcinoma cells conferring protection against the CYP3A and CYP2C8 substrate paclitaxel through metabolic degradation. Inhibition of CYP3A isozymes restores the cells sensitivity to paclitaxel. The combination of gemcitabine and nab-paclitaxel is an established regimen for the treatment of metastasized or locally advanced inoperable pancreatic cancer. Cobicistat is a CYP3A inhibitor developed for the pharmacoenhancement of protease inhibitors. The addition of cobicistat to gemcitabine and nab-paclitaxel may increase the antitumor effect. We will conduct a phase I dose escalation trial with a classical 3 + 3 design to investigate the safety, tolerability, and pharmacokinetics (PKs) of gemcitabine, nab-paclitaxel, and cobicistat. Although the doses of gemcitabine (1000 mg/m2 ) and cobicistat (150 mg) are fixed, three dose levels of nab-paclitaxel (75, 100, and 125 mg/m2 ) will be explored to account for a potential PK drug interaction. After the dose escalation phase, we will set the recommended dose for expansion (RDE) and treat up to nine patients in an expansion part of the trial. The trial is registered under the following identifiers EudraCT-Nr. 2019-001439-29, drks.de: DRKS00029409, and ct.gov: NCT05494866. Overcoming resistance to paclitaxel by CYP3A5 inhibition may lead to an increased efficacy of the gemcitabine and nab-paclitaxel regimen. Safety, efficacy, PK, and RDE data need to be acquired before investigating this combination in a large-scale clinical study.