Real-life effectiveness of prehabilitation to improve postoperative outcomes in patients with colorectal cancer approaching surgery: A systematic review and meta-analyses of observational studies versus randomized controlled trials.

INTRODUCTION: Current evidence synthesis of prehabilitation studies in colorectal surgery is based on results of randomized controlled trials (RCT). Although RCTs are the gold standard for effectiveness research, observational studies probably better reflect real-life practice. The aims of the current study were to compare observational studies to RCTs regarding the association between prehabilitation and postoperative outcomes, and characteristics of included patients and interventions. METHODS: A systematic search was conducted in PubMed, Embase, and CINAHL (until September 2023). Observational studies and RCTs investigating prehabilitation before colorectal surgery and reporting postoperative complications and/or length of stay (LoS) were included. Two reviewers independently assessed the risk of bias using the Cochrane Risk of Bias 2 tool for RCTs and the Cochrane ROBINS-I tool for observational studies. Meta(regression)-analyses were performed for postoperative complications and LoS. RESULTS: Pooled results showed a statistically significant reduction in postoperative complications (OR 0.54; 95 % confidence interval (CI) 0.40 to 0.72) and LoS (mean difference (MD) -1.34 CI -2.57 to -0.12) after prehabilitation in observational studies but not in RCTs (complications OR 0.95; CI 0.53 to 1.72; LoS MD 0.16 CI -0.52 to 0.83). Patients included in observational studies were older and more often had an ASA score ≥3. In a meta-regression analysis, these characteristics were not statistically significantly associated with the main outcomes. CONCLUSION: Observational studies in a real-life setting showed that prehabilitation can reduce postoperative complications and LoS. To further explore the real-life effectiveness of prehabilitation, specific observational study designs, like a target emulation trial could be used.

The risk of fragility fractures in men with prostate cancer treated with androgen deprivation therapy.

Androgen Deprivation Therapy (ADT) increases long-term fracture risk in prostate cancer. Our study showed a higher fracture risk within six months of ADT use, and current use was associated with a higher risk of fragility fractures. Attention is needed for the prevention of fragility fractures at the start of ADT. PURPOSE: Androgen Deprivation Therapy (ADT) is known to increase long-term fracture risk in men with prostate cancer (PCa), although the risk of fragility fractures remains unclear. This study aims to evaluate the risk of fragility and malignancy-related fractures in men with PCa treated with ADT. METHODS: We conducted a retrospective cohort study of men with PCa. Follow-up time was divided into 30-day intervals and exposure (current, past, or no-ADT use). Current ADT use was stratified by duration of ADT use (≤ 182 days, 183-730 days, and > 730 days). Cause-specific Cox proportional hazard models were used to estimate the risk of fractures. RESULTS: We included 471 patients (mean age 70.5 (± 8.3) years). The mean follow-up time was 5.0 (± 1.7) years in patients who never started ADT, 3.4 (± 2.3) years and 4.1 (± 2.0) years in patients who started ADT at baseline and during follow-up, respectively. In total, 60 patients had a fracture, 48 (80%) fragility, and 12 (20%) malignancy-related fractures. Current ADT use was associated with a higher risk of all fractures (HR 5.10, 95% CI 2.34-11.13) and fragility fractures (HR 3.61, 95% CI 1.57-8.30). The association with malignancy-related fractures could not be studied due to no events during no-ADT use. There was an increased risk of all fractures with longer duration of ADT use. CONCLUSIONS: Current ADT use was associated with a higher risk of fragility fractures than no-ADT use. A higher fracture risk was observed within the first six months of ADT use and persisted for longer durations.

Validation of an automated segmentation method for body composition analysis in colorectal cancer patients using diagnostic abdominal computed tomography images.

BACKGROUND & AIMS: Several automated programs have been developed to facilitate body composition analysis of images from abdominal computed tomography (CT) scans. External validation in patients with colorectal cancer is necessary for use in research and clinical practice. Our aim was to validate an automatic method (AutoMATiCA) of segmenting CT images at the third lumbar level (L3) from patients with colorectal cancer, by comparing with manual segmentation. METHODS: Diagnostic abdominal CT scans of consecutive patients with stage I-III colorectal cancer were analysed to measure cross-sectional areas and tissue densities of skeletal muscle and intra-muscular, visceral, and subcutaneous adipose tissue. Trained analysts performed manual segmentation of L3 CT images using SliceOmatic. Automatic segmentation was performed using AutoMATiCA, an open-source software. The Dice similarity coefficient (DSC) was calculated to assess segmentation accuracy. Agreement of automatic with manual segmentation was evaluated using intra-class correlation coefficients (ICCs) and Bland-Altman plots with limits of agreement. RESULTS: A total of 292 scans were included, of which 62% were from male patients. The agreement of AutoMATiCA with the manual segmentation was excellent, with median DSC values ranging from 0.900 to 0.991 and ICCs above 0.95 for all segmented areas. No systematic deviations were observed in Bland-Altman plots for all segmented areas, with overall narrow limits of agreement. CONCLUSIONS: AutoMATiCA provides an accurate segmentation of abdominal CT images from patients with colorectal cancer. Our findings support its use as a highly efficient automated tool for body composition analysis in research and potentially also in clinical practice.

Development of a Multidisciplinary Care Pathway for Fracture Prevention in Men with Prostate Cancer at Initiation of Androgen Deprivation Therapy.

Fracture risk is increased in men with prostate cancer (PCa) receiving Androgen Deprivation Therapy (ADT). However, routine assessment of fracture risk is often not systematically applied. We aimed to establish a comprehensive care pathway for fracture prevention in men with PCa starting ADT. Therefore, a multidisciplinary working group designed and implemented a care pathway using the 'Knowledge to Action' framework, based on current Dutch guidelines for PCa, osteoporosis and fracture prevention, and an extensive literature review of other guidelines. The pathway was developed according to a five-step clinical approach including case finding, fracture risk assessment based on risk factors, bone mineral density test, vertebral fracture assessment, differential diagnosis, treatment, and annual follow-up. Our fracture prevention care pathway for patients with PCa at the time of ADT initiation was designed to promote a patient-centered, multidisciplinary approach to facilitate the implementation of early fracture prevention measures.

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/ ).

Longitudinal associations of plasma kynurenines and ratios with fatigue and quality of life in colorectal cancer survivors up to 12 months post-treatment.

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health-related quality of life (HRQoL). Inflammation-induced activation of the kynurenine pathway may play a role in cancer-related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Repeated measurements at 6 weeks, 6 months, and 12 months post-treatment were performed in 249 stage I-III CRC survivors. Plasma tryptophan and eight kynurenines were analyzed using liquid chromatography-tandem mass spectrometry (LC/MS-MS). Fatigue and HRQoL outcomes were evaluated using validated questionnaires. Confounder-adjusted linear mixed models were conducted to analyze longitudinal associations, with false discovery rate (FDR) correction. Higher tryptophan (Trp), kynurenic acid (KA), and xanthurenic acid (XA) concentrations, as well as a higher kynurenic acid-to-quinolinic acid ratio (KA/QA), were associated with less fatigue and better functioning, while a higher kynurenine-to-tryptophan ratio (KTR) and 3-hydroxykynurenine ratio (HKr) were associated with more fatigue and worse functioning. Finally, higher KA and XA concentrations and a higher KA/QA ratio were associated with a higher overall HRQoL summary score, while a higher HKr was associated with a lower overall HRQoL summary score. In conclusion, we observed that tryptophan and several kynurenines were longitudinally associated with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Future research is needed to validate our findings and explore the potential of the kynurenine pathway as intervention target for reducing fatigue and enhancing HRQoL after CRC treatment.

Longitudinal associations of plasma kynurenines and ratios with anxiety and depression scores in colorectal cancer survivors up to 12 months post-treatment.

INTRODUCTION: Colorectal cancer (CRC) survivors often experience neuropsychological symptoms, including anxiety and depression. Mounting evidence suggests a role for the kynurenine pathway in these symptoms due to potential neuroprotective and neurotoxic roles of involved metabolites. However, evidence remains inconclusive and insufficient in cancer survivors. Thus, we aimed to explore longitudinal associations of plasma tryptophan, kynurenines, and their established ratios with anxiety and depression in CRC survivors up to 12 months post-treatment. METHODS: In 249 stage I-III CRC survivors, blood samples were collected at 6 weeks, 6 months, and 12 months post-treatment to analyze plasma concentrations of tryptophan and kynurenines using liquid-chromatography tandem-mass spectrometry (LC/MS-MS). At the same timepoints, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Confounder-adjusted linear mixed models were used to analyze longitudinal associations. Sensitivity analyses with false discovery rate (FDR) correction were conducted to adjust for multiple testing. RESULTS: Higher plasma tryptophan concentrations were associated with lower depression scores (ß as change in depression score per 1 SD increase in the ln-transformed kynurenine concentration: -0.31; 95%CI: -0.56,-0.05), and higher plasma 3-hydroxyanthranilic acid concentrations with lower anxiety scores (-0.26; -0.52,-0.01). A higher 3-hydroxykynurenine ratio (HKr; the ratio of 3-hydroxykynurenine to the sum of kynurenic acid, xanthurenic acid, anthranilic acid, and 3-hydroxyanthranilic acid) was associated with higher depression scores (0.34; 0.04,0.63) and higher total anxiety and depression scores (0.53; 0.02,1.04). Overall associations appeared to be mainly driven by inter-individual associations, which were statistically significant for tryptophan with depression (-0.60; -1.12,-0.09), xanthurenic acid with total anxiety and depression (-1.04; -1.99,-0.10), anxiety (-0.51; -1.01,-0.01), and depression (-0.56; -1.08,-0.05), and kynurenic-acid-to-quinolinic-acid ratio with depression (-0.47; -0.93,-0.01). In sensitivity analyses, associations did not remain statistically significant after FDR adjustment. CONCLUSION: We observed that plasma concentrations of tryptophan, 3-hydroxyanthranilic acid, xanthurenic acid, 3-hydroxykynurenine ratio, and kynurenic-acid-to-quinolinic-acid ratio tended to be longitudinally associated with anxiety and depression in CRC survivors up to 12 months post-treatment. Future studies are warranted to further elucidate the association of plasma kynurenines with anxiety and depression.

Longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in colorectal cancer survivors up to 24 months post-treatment.

Fatigue and insomnia, potentially induced by inflammation, are distressing symptoms experienced by colorectal cancer (CRC) survivors. Emerging evidence suggests that besides the nutritional quality and quantity, also the timing, frequency and regularity of dietary intake (chrono-nutrition) could be important for alleviating these symptoms. We investigated longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in CRC survivors. In a prospective cohort of 459 stage I-III CRC survivors, four repeated measurements were performed between 6 weeks and 24 months post-treatment. Chrono-nutrition variables included meal energy contribution, frequency (a maximum of six meals could be reported each day), irregularity and time window (TW) of energetic intake, operationalised based on 7-d dietary records. Outcomes included sleep quality, fatigue and plasma concentrations of inflammatory markers. Longitudinal associations of chrono-nutrition variables with outcomes from 6 weeks until 24 months post-treatment were analysed by confounder-adjusted linear mixed models, including hybrid models to disentangle intra-individual changes from inter-individual differences over time. An hour longer TW of energetic intake between individuals was associated with less fatigue (ß: -6·1; 95 % CI (-8·8, -3·3)) and insomnia (ß: -4·8; 95 % CI (-7·4, -2·1)). A higher meal frequency of on average 0·6 meals/d between individuals was associated with less fatigue (ß: -3·7; 95 % CI (-6·6, -0·8)). An hour increase in TW of energetic intake within individuals was associated with less insomnia (ß: -3·0; 95 % CI (-5·2, -0·8)) and inflammation (ß: -0·1; 95 % CI (-0·1, 0·0)). Our results suggest that longer TWs of energetic intake and higher meal frequencies may be associated with less fatigue, insomnia and inflammation among CRC survivors. Future studies with larger contrasts in chrono-nutrition variables are needed to confirm these findings.

Treatment interval in curative treatment of colon cancer, does it impact (cancer free) survival? A non-inferiority analysis.

BACKGROUND: In treatment of colon cancer, strict waiting-time targets are enforced, leaving professionals no room to lengthen treatment intervals when advisable, for instance to optimise a patient's health status by means of prehabilitation. Good quality studies supporting these targets are lacking. With this study we aim to establish whether a prolonged treatment interval is associated with a clinically relevant deterioration in overall and cancer free survival. METHODS: This retrospective multicenter non-inferiority study includes all consecutive patients who underwent elective oncological resection of a biopsy-proven primary non-metastatic colon carcinoma between 2010 and 2016 in six hospitals in the Southern Netherlands. Treatment interval was defined as time between diagnosis and surgical treatment. Cut-off points for treatment interval were ≤35 days and ≤49 days. FINDINGS: 3376 patients were included. Cancer recurred in 505 patients (15.0%) For cancer free survival, a treatment interval >35 days and >49 days was non-inferior to a treatment interval ≤35 days. Results for overall survival were inconclusive, but no association was found. CONCLUSION: For cancer free survival, a prolonged treatment interval, even over 49 days, is non-inferior to the currently set waiting-time target of ≤35 days. Therefore, the waiting-time targets set as fundamental objective in current treatment guidelines should become directional instead of strict targets.

A retrospective analysis of the association of effort-independent cardiopulmonary exercise test variables with postoperative complications in patients who underwent elective colorectal surgery.

PURPOSE: This study aimed to investigate the association of effort-independent variables derived from the preoperative cardiopulmonary exercise test (CPET) with 30-day postoperative complications after elective colorectal surgery. METHODS: A multicenter (n=4) retrospective explorative study was performed using data of patients who completed a preoperative CPET and underwent elective colorectal surgery. The preoperative slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2-slope) and the oxygen uptake efficiency slope (OUES), as well as 30-day postoperative complications, were assessed. Multivariable logistic regression analyses and receiver operating characteristic (ROC) curves were used to investigate the prognostic value of the relationship between these preoperative CPET-derived effort-independent variables and postoperative complications. RESULTS: Data from 102 patients (60.1% males) with a median age of 72.0 (interquartile range 67.8-77.4) years were analyzed. Forty-four patients (43.1%) had one or more postoperative complications (of which 52.3% general and 77.3% surgical complications). Merely 10 (9.8%) patients had a general complication only. In multivariate analysis adjusted for surgical approach (open versus minimally invasive surgery), the VE/VCO2-slope (odds ratio (OR) 1.08, confidence interval (CI) 1.02-1.16) and OUES (OR 0.94, CI 0.89-1.00) were statistically significant associated with the occurrence of 30-day postoperative complications. CONCLUSION: The effort-independent VE/VCO2-slope and OUES might be used to assist in future preoperative risk assessment and could especially be of added value in patients who are unable or unwilling to deliver a maximal cardiorespiratory effort. Future research should reveal the predictive value of these variables individually and/or in combination with other prognostic (CPET-derived) variables for postoperative complications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05331196.

Cardiac and intramuscular adaptations following short-term exercise prehabilitation in unfit patients scheduled to undergo hepatic or pancreatic surgery: study protocol of a multinuclear MRI study.

INTRODUCTION: Short-term exercise prehabilitation programmes have demonstrated promising results in improving aerobic capacity of unfit patients prior to major abdominal surgery. However, little is known about the cardiac and skeletal muscle adaptations explaining the improvement in aerobic capacity following short-term exercise prehabilitation. METHODS AND ANALYSIS: In this single-centre study with a pretest-post-test design, 12 unfit patients with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/kg/min and/or VO2 at peak exercise ≤18 mL/kg/min, who are scheduled to undergo hepatopancreatobiliary surgery at the University Medical Center Groningen (UMCG), the Netherlands, will be recruited. As part of standard care, unfit patients are advised to participate in a home-based exercise prehabilitation programme, comprising high-intensity interval training and functional exercises three times per week, combined with nutritional support, during a 4-week period. Pre-intervention and post-intervention, patients will complete a cardiopulmonary exercise test. Next to this, study participants will perform additional in-vivo exercise cardiac magnetic resonance (MR) imaging and phosphorus 31-MR spectroscopy of the quadriceps femoris muscle before and after the intervention to assess the effect on respectively cardiac and skeletal muscle function. ETHICS AND DISSEMINATION: This study was approved in May 2023 by the Medical Research Ethics Committee of the UMCG (registration number NL83611.042.23, March 2023) and is registered in the ClinicalTrials.gov register. Results of this study will be submitted for presentation at (inter)national congresses and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05772819.

Longitudinal associations of macronutrient and micronutrient intake with plasma kynurenines in colorectal cancer survivors up to 12 months posttreatment.

BACKGROUND: The tryptophan-kynurenine pathway is increasingly recognized to play a role in health-related quality of life (HRQoL) after cancer. Because tryptophan is an essential amino acid, and vitamins and minerals act as enzymatic cofactors in the tryptophan-kynurenine pathway, a link between diet and kynurenines is plausible. OBJECTIVES: This study aimed to investigate the longitudinal associations of macronutrient and micronutrient intake with metabolites of the kynurenine pathway in colorectal cancer (CRC) survivors up to 12 mo posttreatment. METHODS: In a prospective cohort of stage I-III CRC survivors (n = 247), repeated measurements were performed at 6 wk, 6 mo, and 12 mo posttreatment. Macronutrient and micronutrient intake was measured by 7-d dietary records. Plasma concentrations of tryptophan and kynurenines were analyzed using liquid chromatography tandem mass spectrometry (LC/MS-MS). Longitudinal associations were analyzed using linear mixed models adjusted for sociodemographic, clinical, and lifestyle factors. RESULTS: After adjustment for multiple testing, higher total protein intake was positively associated with kynurenic acid (KA) (ß as standard deviation [SD] change in KA concentration per 1 SD increase in total protein intake: 0.12; 95% CI: 0.04, 0.20), xanthurenic acid (XA) (standardized ß: 0.22; 95% CI: 0.11, 0.33), 3-hydroxyanthranilic acid (HAA) (standardized ß: 0.15; 95% CI: 0.04, 0.27) concentrations, and the kynurenic acid-to-quinolinic acid ratio (KA/QA) (standardized ß: 0.12; 95% CI: 0.02,0.22). In contrast, higher total carbohydrate intake was associated with lower XA concentrations (standardized ß: -0.18; 95% CI: -0.30, -0.07), a lower KA/QA (standardized ß: -0.23; 95% CI: -0.34, -0.13), and a higher kynurenine-to-tryptophan ratio (KTR) (standardized ß: 0.20; 95% CI: 0.10, 0.30). Higher fiber intake was associated with a higher KA/QA (standardized ß: 0.11; 95% CI: 0.02, 0.21) and a lower KTR (standardized ß: -0.12; 95% CI: -0.20, -0.03). Higher total fat intake was also associated with higher tryptophan (Trp) concentrations (standardized ß: 0.18; 95% CI: 0.06, 0.30) and a lower KTR (standardized ß: -0.13; 95% CI: -0.22, -0.03). For micronutrients, positive associations were observed for zinc with XA (standardized ß: 0.13; 95% CI: 0.04, 0.21) and 3-hydroxykynurenine (HK) (standardized ß: 0.12; 95% CI: 0.03, 0.20) concentrations and for magnesium with KA/QA (standardized ß: 0.24; 95% CI: 0.13, 0.36). CONCLUSIONS: Our findings show that intake of several macronutrients and micronutrients is associated with some metabolites of the kynurenine pathway in CRC survivors up to 12 mo posttreatment. These results may be relevant for enhancing HRQoL after cancer through potential diet-induced changes in kynurenines. Further studies are necessary to confirm our findings.

Node-negative colon cancer: histological, molecular, and stromal features predicting disease recurrence.

BACKGROUND: Within the group of node-negative colon cancer patients, presumed to have a good prognosis, a significant percentage of patients develops cancer-recurrence. Current high-risk features prove inadequate to select these particular high-risk patients. In the process of tailor-made care and shared decision-making the need to identify these patients grows. In this study we investigate the value of adding molecular markers and the tumour-stroma ratio (TSR) to conventional histological tumour staging methods to improve the selection of high risk patients. METHODS: We retrospectively analysed 201 patients diagnosed with TNM-stage I-II colon cancer and treated by complete oncological resection between November 1st 2002 and December 31st 2012 at the Jeroen Bosch Hospital. Conventional histological tumour staging, BRAF mutations, KRAS mutations, MSI status and TSR were determined. Differences between groups based on TSR and mutation status, in disease free survival were analysed using Cox-Regression analyses. RESULTS: Poorly differentiated histology (p = 0.002), high-TSR (p = 0.033), BRAF-mutation (p = 0.008) and MSI (p = 0.011) were identified as significant risk factors for cancer recurrence. The risk of recurrence increased in the presence of both a BRAF-mutation and high-TSR compared to the absence of both factors or presence of only one factor (HR = 3.66 BRAF-mt/TSR-low (p = 0.006), HR 2.82 BRAF-wt/TSR-high (p = 0.015), HR = 4.39 BRAF-mt/TSR-high (p = 0.023)). This was also seen in tumours with MSI and high-TSR (HR = 2.46 MSS/TSR-high (p = 0.041), HR = 3.31 MSI/TSR-high (p = 0.045). CONCLUSION: Judging by the higher HR for the combination of the prognostic factors TSR and BRAF compared to the HRs of these prognostic factors individually, the prognostication for disease free survival can be improved by determining both TSR and BRAF instead of BRAF alone, as is done in current daily practise. In this study MSI also shows additional value to TSR in the prognostication of disease free survival. Adopting TSR into daily diagnostics will be of additional value next to currently used molecular markers in risk stratification of patients with node negative colon cancer and is therefore advised.

Effects of exercise prehabilitation and/or rehabilitation on health-related quality of life and fatigue in patients with non-small cell lung cancer undergoing surgery: A systematic review.

BACKGROUND: This systematic review aimed to appraise the current available evidence regarding the effects of exercise prehabilitation and rehabilitation on perceived health-related quality of life (HRQoL) and fatigue in patients undergoing surgery for non-small cell lung cancer (NSCLC). METHODS: Studies were selected according to Cochrane guidelines and assessed for methodological quality and therapeutic quality (the international CONsensus on Therapeutic Exercise aNd Training (i-CONTENT)). Eligible studies included patients with NSCLC performing exercise prehabilitation and/or rehabilitation and postoperative HRQoL and fatigue up to 90-days postoperatively. RESULTS: Thirteen studies were included. Exercise prehabilitation and rehabilitation significantly improved postoperative HRQoL in almost half of the studies (47%), although none of the studies demonstrated a decrease in fatigue. Methodological quality and therapeutic quality were poor in respectively 62% and 69% of the studies. CONCLUSION: There was an inconsistent effect of exercise prehabilitation and exercise rehabilitation on improving HRQoL in patients with NSCLC undergoing surgery, with no effect on fatigue. Due to the low methodological and therapeutic quality of included studies, it was not possible to identify the most effective training program content to improve HRQoL and reduce fatigue. It is recommended to investigate the impact of a high therapeutic qualified exercise prehabilitation and exercise rehabilitation on HRQoL and fatigue in larger studies.

Influence of different data-averaging methods on mean values of selected variables derived from preoperative cardiopulmonary exercise testing in patients scheduled for colorectal surgery.

INTRODUCTION: Patients with a low cardiorespiratory fitness (CRF) undergoing colorectal cancer surgery have a high risk for postoperative complications. Cardiopulmonary exercise testing (CPET) to assess CRF is the gold standard for preoperative risk assessment. To aid interpretation of raw breath-by-breath data, different methods of data-averaging can be applied. This study aimed to investigate the influence of different data-averaging intervals on CPET variables used for preoperative risk assessment, as well as to evaluate whether different data-averaging intervals influence preoperative risk assessment. METHODS: A total of 21 preoperative CPETs were interpreted by two exercise physiologists using stationary time-based data-averaging intervals of 10, 20, and 30 seconds and rolling average intervals of 3 and 7 breaths. Mean values of CPET variables between different data averaging intervals were compared using repeated measures ANOVA. The variables of interest were oxygen uptake at peak exercise (VO2peak), oxygen uptake at the ventilatory anaerobic threshold (VO2VAT), oxygen uptake efficiency slope (OUES), the ventilatory equivalent for carbon dioxide at the ventilatory anaerobic threshold (VE/VCO2VAT), and the slope of the relationship between the minute ventilation and carbon dioxide production (VE/VCO2-slope). RESULTS: Between data-averaging intervals, no statistically significant differences were found in the mean values of CPET variables except for the ventilatory equivalent for carbon dioxide at the ventilatory anaerobic threshold (P = 0.001). No statistically significant differences were found in the proportion of patients classified as high or low risk regardless of the used data-averaging interval. CONCLUSION: There appears to be no significant or clinically relevant influence of the evaluated data-averaging intervals on the mean values of CPET outcomes used for preoperative risk assessment. Clinicians may choose a data-averaging interval that is appropriate for optimal interpretation and data visualization of the preoperative CPET. Nevertheless, caution should be taken as the chosen data-averaging interval might lead to substantial within-patient variation for individual patients. CLINICAL TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT05353127).

High prevalence of vertebral fractures at initiation of androgen deprivation therapy for prostate cancer.

Purpose: Treatment of Prostate Cancer (PCa) with Androgen Deprivation Therapy (ADT) involves long-term consequences including bone loss and fractures. Our aim was to evaluate the calculated fracture risk and the prevalence of osteoporosis, vertebral fractures (VF) and sarcopenia in men with PCa at initiation of ADT, as ADT will increase fracture risk from that moment onward. Methods: In this cross-sectional real-world study in men at ADT initiation, fracture risk factors including comorbidities, medication, and 10-year fracture risk (FRAX®) were assessed. Laboratory tests, dual-energy X-ray absorptiometry, and spinal X-rays were performed. Sarcopenia was defined according to EWGSOP2. Results: In 115 men at ADT initiation, aged 73.3 (±7.6) years, osteoporosis was diagnosed in 4.3 % and osteopenia in 35.7 %. The mean 10-year fracture risk of major osteoporotic fracture was 4.4 % and of hip fracture 1.7 %, respectively. At least one VF was present in 32.2 % and 33.9 % of men had osteoporosis and/or a VF assessed on spinal X-rays. In 10.4 % at least one new fracture-risk-associated metabolic bone disorder was diagnosed with laboratory testing. Sarcopenia was diagnosed in only one patient. Conclusions: Although the prevalence of osteoporosis, sarcopenia and 10-years fracture risk is low, there is a high prevalence of vertebral fractures in a third of the men with PCa at the time of ADT initiation. Besides a BMD measurement and fracture risk calculation using FRAX, a systematic vertebral fracture assessment should be considered in all men with PCa at initiation of ADT to provide a reliable baseline classification of VFs to improve identification of true incident VFs during ADT.

The clinical decision-making process of healthcare professionals within a personalized home-based rehabilitation program during sequential chemoradiotherapy for stage III non-small lung cancer: A case study.

INTRODUCTION: The purpose of this case study was to demonstrate the clinical decision-making process of healthcare professionals within a rehabilitation program during chemoradiotherapy (CHRT) for a high-risk patient diagnosed with stage III non-small cell lung cancer (NSCLC). The course of CHRT and patient's preferences, facilitators, and barriers were considered. CASE-DESCRIPTION: The patient was a 69-year-old man with a history of rheumatoid arthritis diagnosed with stage III NSCLC. INTERVENTION: A home-based, personalized, and partly supervised rehabilitation program during CHRT, including aerobic, resistance, and breathing exercises, as well as nutritional counseling. OUTCOMES: The patient suffered from side effects of CHRT, which required adjustments in the context and intensity of the exercises. An important facilitator for the patient was encouraged by his wife in following the home-based rehabilitation program. During home visits, the patient and physiotherapists performed the exercises together to help him to overcome the burden and motivate the patient to adhere to the rehabilitation program. CONCLUSION: This case study demonstrates that physical exercise training could be performed by adjusting training intensity and the way in which the physical exercise training was delivered, while the patient experienced side effects from CHRT. In addition, the involvement and support of (in)formal caregivers seems essential for adherence to rehabilitation.

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 sedentary behavior and physical activity with body composition in colorectal cancer survivors up to 2 years post treatment.

PURPOSE: We investigated longitudinal associations of sedentary behavior, light-intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) with body composition in colorectal cancer (CRC) survivors, between 6 weeks and 24 months post treatment. In addition, we explored whether body composition mediated associations of sedentary behavior and MVPA with fatigue. METHODS: A prospective cohort study was conducted in 459 stage I-III CRC patients recruited at diagnosis. Measurements were performed of accelerometer-assessed sedentary time (hours/day), self-reported LPA and MVPA (hours/week), anthropometric assessment of body mass index (BMI), waist circumference and fat percentage (measures of adiposity), and muscle circumference and handgrip strength (measures of muscle mass/function) repeated at 6 weeks, and 6, 12 and 24 months post treatment. Longitudinal associations of sedentary time and physical activity with body composition were analyzed using confounder-adjusted linear mixed models. Mediation analyses were performed to explore the role of body mass index (BMI) and handgrip strength as mediators in associations of sedentary time and MVPA with fatigue. RESULTS: Less sedentary time and LPA were, independent of MVPA, longitudinally associated with increased handgrip strength, but not with measures of adiposity. More MVPA was associated with increased adiposity and increased handgrip strength. Higher BMI partly mediated associations between higher sedentary time and more fatigue. CONCLUSION: Within the first two years after CRC treatment, changes in sedentary behavior, physical activity and body composition are interrelated and associated with fatigue. Intervention studies are warranted to investigate causality. TRIAL REGISTRATION: The EnCoRe study is registered at trialregister.nl as NL6904 (former ID: NTR7099).

The Association between Diabetes Medication Use and Tumour Characteristics at Diagnosis in Patients with Urothelial Carcinoma: A Retrospective Registry-Based Study.

BACKGROUND: Observational studies indicate a potential association between diabetes medication use and aggressiveness of bladder cancer. OBJECTIVE: The objective is to exploratively study the association between diabetes medication use, as proxy for diabetes, and cancer characteristics of urothelial carcinoma at diagnosis. Furthermore, differences in associations between specific types of diabetes medication are studied. METHODS: The association between use of diabetes medication and urothelial carcinoma (UC) characteristics at diagnosis is studied. A retrospective registry-based study among UC patients in the Netherlands was performed for which two large linked registries from PHARMO and IKNL were used. Patients diagnosed with UC between 2000 and 2016 and no previous cancer were included in this study. In this study, 1,168 UC patients who were diabetes medication users were included as well as 3,609 non-users. Conditional logistic regression analysis was performed to determine odds ratios comparing cancer characteristics between different types of diabetes medication users to non-users. RESULTS: Noninsulin antidiabetic drugs (NIAD) use was associated with a muscle-invasive type of UC compared to non-users (OR = 1.31, 95% CI: 1.10-1.55 for T2+ versus Ta) as well as a poorly differentiated tumour (OR = 1.31, 95% CI: 1.07-1.59 for poorly versus well differentiated tumours). CONCLUSION: Users of diabetes medication are potentially more likely to be diagnosed with a more aggressive tumour than non-users; however, lifestyle factors could not be adjusted for.