Surgical shortening of lengthened iliac arteries in endurance athletes: Short-term and long-term satisfaction.

OBJECTIVE: Endurance athletes are prone to develop flow limitations in iliac arteries (FLIA). Especially in cyclists and ice speed skaters, excessive hemodynamic loading coupled with hip hyperflexion may cause kinking in lengthened iliac arteries necessitating surgical correction. This study investigated the short-term (≤1.5 years) and long-term (≥5 years) satisfaction of operative shortening of the iliac artery in endurance athletes. METHODS: All patients who were diagnosed and operated for FLIA owing to lengthened and kinked iliac arteries between 1997 and 2015 in one center were analyzed. Short-term follow-up consisted of an incremental maximal cycling test, ankle-brachial index with flexed hips, echo-Doppler examination with peak systolic velocity measurements and contrast-enhanced magnetic resonance angiography before and 6 to 18 months after surgery. Both short- and long-term satisfaction were assessed using questionnaires. RESULTS: A total of 83 patients (90 operated legs; 96.7% males; median age of 34 years at the time of surgery; interquartile range [IQR], 29-47) were analyzed. In the short-term, 87.5% reported symptom reduction with an 86.4% overall satisfaction rate. Symptom-free cycling improved from 272 ± 84 W to 384 ± 101 W (P < .001), whereas the maximal workload increased from 419 ± 72 W to 428 ± 67 W (P = .01). The ankle-brachial index with flexed hips increased from 0.55 (IQR, 0.45-0.65) to 0.62 (IQR, 0.52-0.74; P = .008), and the peak systolic velocity measured with hips flexed decreased from 2.50 m/s (IQR, 1.77-3.13 m/s) to 1.57 m/s (IQR, 1.20-2.04 m/s; P < .001). After a median of 12 years (IQR, 9.0-15.4 years), symptoms were still decreased in 84.1% of patients with an 81.2% overall satisfaction rate (79.5% response rate). Three patients needed a reintervention (recurrent FLIA, n = 2; failure, n = 1). CONCLUSIONS: Operative shortening of a lengthened and kinked iliac artery causing FLIA is successful both in the short- and long-term.

Short- and long-term outcomes after endarterectomy with autologous patching in endurance athletes with iliac artery endofibrosis.

OBJECTIVE: Endurance athletes such as cyclists may develop intermittent claudication owing to iliac artery endofibrosis after long-lasting extreme hemodynamic challenges. This study investigated short-term (<1.5 years) and long-term (>5 years) satisfaction and safety after a surgical endarterectomy and autologous patching. METHODS: Data of endurance athletes who underwent an endarterectomy for flow limitation of the iliac artery owing to endofibrosis between 1997 and 2015 in one center were studied. Maximal cycling exercise tests, ankle-brachial index with flexed hips, echo-Doppler examination (peak systolic velocity), and contrast-enhanced magnetic resonance angiography were performed before and 6 to 18 months after surgery. Short-term and long-term satisfaction were evaluated using questionnaires. Potential patch dilatation was assessed using echo-Doppler. RESULTS: Analysis of 68 patients (79 legs; 55.7% males, median age at the time of surgery, 34 years; interquartile range, 26-41 years) demonstrated that cycling workload at symptom onset improved from 226 ± 97 to 333 ± 101 (P < .001) Watts. Peak workload increased from 326 ± 111 to 352 ± 93 Watts (P < .001). Ankle-brachial index with flexed hips increased from 0.34 (interquartile range [IQR], 0.00-0.47) to 0.59 (IQR, 0.51-0.69; P < .001). Peak systolic velocity with extended and flexed hip decreased from 2.04 m·sec-1 (IQR, 1.52-2.56 m·3sec-1) to 1.25 m·sec-1 (IQR, 0.92-1.62 m·sec-1; P < .001) and 2.40 m·sec-1 (IQR, 1.81-2.81 m·sec-1) to 1.15 m·sec-1 (IQR, 0.97-1.60 m·sec-1; P < .001), respectively. Thirty-day major complication rate was 5.1% (hematoma requiring evacuation nLegs = 2, septic bleeding from deep infection nLegs = 1, and iliac occlusion requiring thrombectomy nLegs = 1). In the short term, 91.2% of patients reported symptom reduction with a 93.7% overall satisfaction rate. After a median of 11.1 years (IQR, 7.8-17.6 years), the overall satisfaction was 91.7%; 94.5% of patients reported persistent symptom reduction. Patch dilatation of >20 mm was observed in two patients. Linear mixed model analysis revealed no alarming patch dilatation in the long term. CONCLUSIONS: Endarterectomy with an autologous patch for intermittent claudication owing to iliac artery endofibrosis in endurance athletes shows high rates of patient satisfaction and symptom reduction in both the short and long term. The risk of surgical complications or patch dilatation is mild. A surgical intervention for flow limitation of the iliac artery owing to endofibrosis is safe and successful.

Short- and long-term results of operative iliac artery release in endurance athletes.

OBJECTIVE: Endurance athletes can develop intermittent claudication due to sports-related flow limitations of the iliac artery (FLIA) caused by arterial kinking. In the present study, we investigated the short- and long-term efficacy of an operative release for iliac artery kinking. METHODS: Between 1996 and 2015, all patients with a diagnosis of FLIA due to iliac artery kinking without substantial arterial stenosis (<15%) or an excessive arterial length (vessel length to straight ratio, <1.25) who had undergone surgery were included. The short-term follow-up protocol consisted of cycling tests, the ankle brachial index with a flexed hip, and Doppler echography examinations to determine the peak systolic velocity before and 6 to 18 months after surgery. Additionally, the short- and long-term efficacy were evaluated using questionnaires. RESULTS: A total of 142 endurance athletes (155 legs; 88.4% male; median age, 26 years; interquartile range [IQR], 22-31 years) were available for analysis. In the short term, the symptoms had decreased in 83.9% of the patients, with an overall 80.3% satisfaction rate. Power during a maximal cycling test had improved from 420 W (IQR, 378-465 W) to 437 W (IQR, 392-485 W; P < .001). The symptom-free workload had increased from 300 W (IQR, 240-340 W) to 400 W (IQR, 330-448 W; P < .001). The postexercise ankle brachial index with a flexed hip had increased from 0.53 (IQR, 0.40-0.61) to 0.57 (IQR, 0.47-0.64; P = .002), and the peak systolic velocity with a flexed hip had decreased from 1.88 m/s (IQR, 1.45-2.50 m/s) to 1.52 m/s (IQR, 1.19-2.07 m/s; P < .001). Postoperative imaging studies revealed some degree kinking in 33.9%, mostly asymptomatic. The long-term results were evaluated after a median of 15.2 years (IQR, 10.9-19.5 years). The athletes had cycled an additional 125.500 km (IQR, 72.00-227.500 km), which was approximately equal to the 131.000 km (IQR, 98.250-220.000 km) cycled before the diagnosis of FLIA. On the long term, 63.9% of the athletes reported persistent reduction of complaints, with an overall 59.1% satisfaction rate. Eight patients had required reintervention, six because of treatment failure and two because of newly developed FLIA. CONCLUSIONS: Operative iliac artery release for sports-related functional kinking in the absence of stenosis or an excessive vessel length was effective for most athletes in the short and long term.

Physical Activity is Associated with Health Related Quality of Life in Lymphoma Survivors Regardless of Body Mass Index; Results from the Profiles Registry.

BACKGROUND: Being obese and having a sedentary lifestyle is associated with impaired health-related quality of life (HRQoL) among cancer survivors. The aim of the present study is to investigate the combined influence of body mass index (BMI) and physical activity on HRQoL in lymphoma survivors. METHODS: Lymphoma survivors diagnosed between 1999 and 2012 were invited to complete questionnaires about body height and weight, physical activity and HRQoL using the EORTC QLQ-C30. Multivariable analyses were conducted to evaluate the association of BMI and physical activity on HRQoL. RESULTS: 1.339 lymphoma survivors responded (response rate of 72%) of whom 43% had a healthy weight, 41% were overweight and 14% were obese. They spent on average 10 h, on moderate to vigorous physical activity (MVPA) per week. Multivariable linear regression analysis shows that relatively high active survivors reported higher HRQoL scores and less fatigue compared to relatively low active lymphoma survivors, regardless of BMI. CONCLUSION: MVPA was associated with higher HRQoL in lymphoma survivors regardless of BMI. Further studies, are needed to investigate effects of healthy lifestyle changes to improve HRQoL in lymphoma survivors. Research in understanding association of lifestyle factors may guide future support for lymphoma cancer survivors.

Construct Validity of the Steep Ramp Test for Assessing Cardiorespiratory Fitness in Patients With Breast Cancer and the Effect of Chemotherapy-Related Symptom Burden.

OBJECTIVE: To investigate the construct validity of the Steep Ramp Test (SRT) by longitudinally comparing the correlation between maximum short exercise capacity of the SRT and direct measurements of peak oxygen consumption (Vo2peak) during or shortly after treatment in patients with breast cancer and the potential effect of chemotherapy-induced symptom burden. DESIGN: Cross-sectional. SETTING: Multicenter. PARTICIPANTS: We used data from 2 studies that included women with breast cancer treated with chemotherapy, resulting in 274 observations. A total of 161 patients (N=161) performed the cardiopulmonary exercise test and the SRT in 2 test sessions on different time points around chemotherapy treatment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fatigue was assessed with the Multidimensional Fatigue Inventory, and nausea and vomiting and pain by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The longitudinal correlation between the maximum short exercise capacity and Vo2peak was investigated using a linear mixed model. Interaction terms were added to the model to investigate whether the correlation varied by symptom burden. RESULTS: We found a statistically significant moderate correlation between Vo2peak and maximum short exercise capacity (0.61; 95% confidence interval, 0.51-0.70; P<.01) over time. This correlation was slightly attenuated (-0.07; 95% confidence interval, -0.13 to 0.00; P=.04) in patients with chemotherapy-related nausea and vomiting, indicating smaller correlations of Vo2peak with the maximum short exercise capacity with increasing symptom burden. Pain and fatigue did not significantly modify the correlation. CONCLUSIONS: The SRT can only be used as a proxy for changes in aerobic capacity with great caution and with attention for the level of nausea and vomiting.

The effect of additional protein on lean body mass preservation in post-bariatric surgery patients: a systematic review.

BACKGROUND: As result of bariatric surgery, patients are susceptible to protein deficiency which can result in undesirable lean body mass (LBM) loss. Consumption of high-protein diets or supplements could counteract this, but evidence about the effect is scarce. This paper systematically reviewed the literature to determine the effect of additional protein intake (≥60 g/day) on LBM preservation in post-bariatric patients. METHODS: An electronic search of PubMed, EMBASE and the Cochrane Library was conducted. Studies were included if patients received a high-protein diet or protein supplements for at least one month, and LBM was assessed. The primary outcome was difference in mean LBM loss between the experimental (protein) and control group. Secondary outcomes were differences in body fat mass, total body water, body mass index and resting metabolic rate. RESULTS: Two of the five included studies (n = 223) showed that consumption of proteins resulted in significant LBM preservation. Only one study reported a significant difference in the reduction of body fat mass and resting metabolic rate in favour of a high-protein diet, but none of the studies showed a significant difference in total body water loss or body mass index change between the two groups. CONCLUSIONS: This paper showed inconclusive evidence for LBM preservation due to protein supplementation or a high-protein diet in post-bariatric patients. This outcome might be subjected to certain limitations, including a lack of blinding and a low compliance rate reported in the included studies. More specific and personalized recommendations regarding protein intake may need to be established by high quality research. Studies investigating the quantity (g/day) and quality (whey, casein or soy) of proteins are also needed.

Protease-activated receptors are potential regulators in the development of arterial endofibrosis in high-performance athletes.

OBJECTIVE: High-performance athletes can develop symptomatic arterial flow restriction during exercise caused by endofibrosis. The pathogenesis is poorly understood; however, coagulation enzymes, such as tissue factor (TF) and coagulation factor Xa, might contribute to the fibrotic process, which is mainly regulated through activation of protease-activated receptors (PARs). Therefore, the aim of this explorative study was to evaluate the presence of coagulation factors and PARs in endofibrotic tissue, which might be indicative of their potential role in the natural development of endofibrosis. METHODS: External iliac arterial specimens with endofibrosis (n = 19) were collected during surgical interventions. As control, arterial segments of the external iliac artery (n = 20) were collected post mortem from individuals with no medical history of cardiovascular disease who donated their body to medical science. Arteries were paraffinized and cut in tissue sections for immunohistochemical analysis. Positive staining within lesions was determined with ImageJ software (National Institutes of Health, Bethesda, Md). RESULTS: Endofibrotic segments contained a neointima, causing intraluminal stenosis, which was highly positive for collagen (+150%; P < .01) and elastin (+148%; P < .01) in comparison with controls. Intriguingly, endofibrosis was not limited to the intima because collagen (+213%) and elastin (+215%) were also significantly elevated in the media layer of endofibrotic segments. These findings were accompanied by significantly increased α-smooth muscle actin-positive cells, morphologically compatible with the presence of myofibroblasts. In addition, PAR1 and PAR4 and the membrane receptor TF were increased as well as coagulation factor X. CONCLUSIONS: We showed that myofibroblasts and the accompanying collagen and elastin synthesis might be key factors in the development of endofibrosis. The special association with increased presence of PARs, factor X, and TF suggests that protease-mediated cell signaling could be a contributing component in the mechanisms leading to endofibrosis.

Multimodal prehabilitation in colorectal cancer patients to improve functional capacity and reduce postoperative complications: the first international randomized controlled trial for multimodal prehabilitation.

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients' functional capacity and postoperative complications. METHODS/DESIGN: This international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis. DISCUSSION: Multimodal prehabilitation is expected to enhance patients' functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer. TRIAL REGISTRATION: Trial Registry: NTR5947 - date of registration: 1 August 2016.

Validation and Refinement of Prediction Models to Estimate Exercise Capacity in Cancer Survivors Using the Steep Ramp Test.

OBJECTIVE: To further test the validity and clinical usefulness of the steep ramp test (SRT) in estimating exercise tolerance in cancer survivors by external validation and extension of previously published prediction models for peak oxygen consumption (Vo2peak) and peak power output (Wpeak). DESIGN: Cross-sectional study. SETTING: Multicenter. PARTICIPANTS: Cancer survivors (N=283) in 2 randomized controlled exercise trials. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prediction model accuracy was assessed by intraclass correlation coefficients (ICCs) and limits of agreement (LOA). Multiple linear regression was used for model extension. Clinical performance was judged by the percentage of accurate endurance exercise prescriptions. RESULTS: ICCs of SRT-predicted Vo2peak and Wpeak with these values as obtained by the cardiopulmonary exercise test were .61 and .73, respectively, using the previously published prediction models. 95% LOA were ±705mL/min with a bias of 190mL/min for Vo2peak and ±59W with a bias of 5W for Wpeak. Modest improvements were obtained by adding body weight and sex to the regression equation for the prediction of Vo2peak (ICC, .73; 95% LOA, ±608mL/min) and by adding age, height, and sex for the prediction of Wpeak (ICC, .81; 95% LOA, ±48W). Accuracy of endurance exercise prescription improved from 57% accurate prescriptions to 68% accurate prescriptions with the new prediction model for Wpeak. CONCLUSIONS: Predictions of Vo2peak and Wpeak based on the SRT are adequate at the group level, but insufficiently accurate in individual patients. The multivariable prediction model for Wpeak can be used cautiously (eg, supplemented with a Borg score) to aid endurance exercise prescription.

Participation in and adherence to physical exercise after completion of primary cancer treatment.

BACKGROUND: The purpose of this study was  to identify demographic, clinical, psychosocial, physical and environmental factors that are associated with participation in and adherence to a combined resistance and endurance exercise program among cancer survivors, shortly after completion of primary cancer treatment. Data from the randomized controlled Resistance and Endurance exercise After ChemoTherapy (REACT) study were used for this study. METHODS: The participants of the REACT study were randomly allocated to either a high intensity (HI) or low-to-moderate intensity (LMI) exercise program. Patients' participation rate was defined as the cancer survivors' decision to participate in the REACT study. Exercise adherence reflected participants' attendance to the scheduled exercise sessions and their compliance to the prescribed exercises. High session attendance rates were defined as attending at least 80 % of the sessions. High compliance rates were defined as performing at least of 90 % of the prescribed exercise across all sessions. Correlates of exercise adherence were studied separately for HI and LMI exercise. Demographic, clinical, and physical factors were assessed using self-reported questionnaires. Relevant clinical information was extracted from medical records. Multivariable logistic regression analyses were applied to identify correlates that were significantly associated with participation, high session attendance, high compliance with resistance and high compliance with endurance exercises. RESULTS: Participants were more likely to have higher education, be non-smokers, have lower psychological distress, higher outcome expectations, and perceive more exercise barriers than non-participants. In HI exercise, higher self-efficacy was significantly associated with high session attendance and high compliance with endurance exercises, and lower psychological distress was significantly associated with high compliance with resistance exercises. In LMI exercise, being a non-smoker was significantly associated with high compliance with resistance exercises and higher BMI was significantly associated with high compliance with resistance and endurance exercises. Furthermore, breast cancer survivors were less likely to report high compliance with resistance and endurance exercises in LMI exercise compared to survivors of other types of cancer. The discriminative ability of the multivariable models ranged from 0.62 to 0.75. CONCLUSION: Several demographic, clinical and psychosocial factors were associated with participation in and adherence to exercise among cancer survivors. Psychosocial factors were more strongly associated with adherence in HI than LMI exercise. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Register [ NTR2153 ] on the 5(th) of January 2010.

The effect of training during treatment with chemotherapy on muscle strength and endurance capacity: A systematic review.

Background Treatment of cancer with chemotherapy decreases endurance capacity and muscle strength. Training during chemotherapy might prevent this. There are no clear guidelines concerning which type of training and which training dose are effective. This review aims to gain insight into the different training modalities during chemotherapy and the effects of such training to improve endurance capacity and muscle strength in order to obtain the knowledge to compose a future training program which trains cancer patients in the most effective way. Material and methods A systematic search of PubMed was carried out. In total, 809 studies of randomized controlled trials studying the effects of training during chemotherapy on endurance capacity and muscle strength were considered. Only 14 studies met all the inclusion criteria. The studies were assessed on methodological quality by using Cochrane criteria for randomized controlled trials. Results The quality of the studies was generally poor and the study populations varied considerably as the training programs were very heterogeneous. Variables of endurance capacity reported beneficial effects in 10 groups (59%). Increases due to training ranged from 8% to 31%. Endurance capacity decreased in nine of 13 control groups (69%), which ranged from 1% to 32%. Muscle strength improved significantly in 17 of 18 intervention groups (94%), ranging from 2% to 38%. Muscle strength also improved in 11 of 14 control groups (79%), but this increase was only minimal, ranging from 1.3% to 6.5%. Conclusions This review indicates that training during chemotherapy may help in preventing the decrease in muscle strength and endurance capacity. It is important to know which training intensity and duration is the most effective in training cancer patients, to provide a training program suitable for every cancer patient. Training should be based on good research and should be implemented into international guidelines and daily practice. More research is needed.

Randomized controlled trial of the effects of high intensity and low-to-moderate intensity exercise on physical fitness and fatigue in cancer survivors: results of the Resistance and Endurance exercise After ChemoTherapy (REACT) study.

BACKGROUND: International evidence-based guidelines recommend physical exercise to form part of standard care for all cancer survivors. However, at present, the optimum exercise intensity is unclear. Therefore, we aimed to evaluate the effectiveness of a high intensity (HI) and low-to-moderate intensity (LMI) resistance and endurance exercise program compared with a wait list control (WLC) group on physical fitness and fatigue in a mixed group of cancer survivors who completed primary cancer treatment, including chemotherapy. METHODS: Overall, 277 cancer survivors were randomized to 12 weeks of HI exercise (n = 91), LMI exercise (n = 95), or WLC (n = 91). Both interventions were identical with respect to exercise type, duration and frequency, and only differed in intensity. Measurements were performed at baseline (4-6 weeks after primary treatment) and post-intervention. The primary outcomes were cardiorespiratory fitness (peakVO2), muscle strength (grip strength and 30-second chair-stand test), and self-reported fatigue (Multidimensional Fatigue Inventory; MFI). Secondary outcomes included health-related quality of life, physical activity, daily functioning, body composition, mood, and sleep disturbances. Multilevel linear regression analyses were performed to estimate intervention effects using an intention-to-treat principle. RESULTS: In the HI and LMI groups, 74 % and 70 % of the participants attended more than 80 % of the prescribed exercise sessions, respectively (P = 0.53). HI (ß = 2.2; 95 % CI, 1.2-3.1) and LMI (ß = 1.3; 95 % CI, 0.3-2.3) exercise showed significantly larger improvements in peakVO2 compared to WLC. Improvements in peakVO2 were larger for HI than LMI exercise (ß = 0.9; 95 % CI, -0.1 to 1.9), but the difference was not statistically significant (P = 0.08). No intervention effects were found for grip strength and the 30-second chair-stand test. HI and LMI exercise significantly reduced general and physical fatigue and reduced activity (MFI subscales) compared to WLC, with no significant differences between both interventions. Finally, compared to WLC, we found benefits in global quality of life and anxiety after HI exercise, improved physical functioning after HI and LMI exercise, and less problems at work after LMI exercise. CONCLUSIONS: Shortly after completion of cancer treatment, both HI and LMI exercise were safe and effective. There may be a dose-response relationship between exercise intensity and peakVO2, favoring HI exercise. HI and LMI exercise were equally effective in reducing general and physical fatigue. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Register [ NTR2153 ] on the 5th of January 2010.

High levels of physical activity are associated with lower levels of fatigue among lymphoma patients: Results from the longitudinal PROFILES registry.

BACKGROUND: Studies show a cross-sectional association between physical activity (PA) and fatigue among lymphoma cancer patients. However, few longitudinal studies have examined whether PA has a sustained effect on fatigue over time. PURPOSE: To examine the longitudinal relationship between PA and fatigue. METHODS: All living individuals diagnosed with lymphoma between 1999 and 2010 as registered by the Dutch population-based Eindhoven Cancer Registry received a questionnaire on three time points. Generalized linear mixed models were used to estimate the independent effects of PA on fatigue. RESULTS: PA and fatigue levels did not differ between patients short-term (< 1 year) and long-term after diagnosis (1-5 years or > 5 years). PA behavior was relatively constant over time with 84% of the patients meeting the Dutch PA guidelines at all assessment periods. Fatigue scores also remained fairly stable over time with 46% of the patients never being fatigued and 29% always being fatigued. Multivariate analyses showed that patients who met the PA guidelines scored 6.2 (95% CI 3.1-9.2) points lower on total fatigue over time (between subject effect; p < 0.01), compared to patients not meeting PA guidelines. CONCLUSION: During a period of two years, PA and fatigue levels were rather stable within lymphoma patients. Patients who met the PA guidelines reported lower levels of fatigue compared to those not meeting the guidelines, which appeared to be a constant association over time. The observed association between PA and fatigue underlines the importance to focus upon physical training in the care of cancer patients.

Variation in fatigue among 6011 (long-term) cancer survivors and a normative population: a study from the population-based PROFILES registry.

PURPOSE: Cancer survivors commonly experience fatigue, related to disease and its treatment. This study aimed to compare fatigue severity among survivors of different cancer types with a normative population and also to identify variations in fatigue among cancer survivors according to clinical and demographic variables. METHODS: We used cancer survivorship data from the population-based PROFILES registry. We included survivors of endometrial (EC, n = 741) or colorectal cancer (CRC, n = 3878) (1998-2007), thyroid cancer (TC, n = 306) (1990-2008), Hodgkin (HL, n = 150) or non-Hodgkin lymphoma (NHL, n = 716), or multiple myeloma (MM, n = 120) (1999-2008). A representative Dutch normative population (n = 2040) was also assessed. Participants completed the Fatigue Assessment Scale. RESULTS: Cancer survivors were more often classified as fatigued (EC/CRC 39%, HL 40%, NHL 43%, MM 51%, TC 44%) compared with the normative population (21 %; p < 0.001). MM survivors were more often classified as fatigued than all other cancer groups, except NHL (overall p = 0.02). Shorter times since diagnosis (<5 years, 41 versus 38%; p < 0.05), younger age (≤65 years, 42 versus 39%; p < 0.01), being female (43 versus 36%; p < 0.01), chemotherapy treatment (43 versus 39%; p < 0.01), comorbidity (no (27%) versus 1 (35%) versus ≥2 (52%); p < 0.01), educational level (low (44%) versus medium (41%) versus high (32%); p < 0.01), and absence of a partner (47 versus 38%; p < 0.01) were associated with fatigue. CONCLUSIONS: Fatigue levels are substantial in (long-term) cancer survivors and vary depending on cancer type, time since diagnosis, age, gender, treatment with chemotherapy, number of comorbid conditions, educational level, and partnership. Since significantly more cancer survivors feel fatigued in comparison with the normative population, appropriate information, assessment, and interventions for fatigue are needed during or after oncologic treatment. Furthermore, focus on better control or management of comorbid conditions of cancer survivors is recommended.

Bicycle testing as an alternative diagnostic tool in patients suspected of intermittent claudication.

BACKGROUND: The ankle-brachial index (ABI) obtained after a treadmill challenge is often used to confirm the diagnosis of intermittent claudication (IC). However, some patients fail treadmill testing due to (temporary) orthopedic or neurologic comorbidity or fear of falling. The aim of this study was to evaluate the role of bicycle testing as an alternative for treadmill testing. It was hypothesized that ABIs obtained after bicycle tests were not different compared with values after standard treadmill testing. METHODS: In this validation study, newly diagnosed IC patients (Rutherford 1-3) underwent a standard treadmill test (TT, "gold standard") and two bicycle protocols, one with a continuous resistance submaximal character (submaximal bicycle test, SBT) and a second with an incremental ramp form having a maximal character (maximal bicycle test, MBT). ABIs of both legs were obtained before and twice after each of these three different exercise tests. Healthy individuals matched for age and gender served as controls. RESULTS: The study population consisted of 32 patients (68 ± 11 years, 21 men). ABIs of each leg (n = 64) obtained after TT correlated significantly with values obtained after either bicycle test (TT vs. SBT: r = 0.90, P < 0.001; TT vs. MBT: r = 0.88, P < 0.001). Drops in ABI after both types of exercise were significantly correlated (TT vs. SBT: r = 0.66, P < 0.001; TT vs. MBT: r = 0.32, P < 0.01). A 98% sensitivity and 86% specificity for diagnosis of IC was observed after the SBT. After the MBT, these values were 98% and 43%, respectively. Healthy controls (n = 13) demonstrated ABI values >0.9 after cycling in all tests. CONCLUSIONS: Both submaximal and a maximal bicycle tests may serve as alternative noninvasive tools for detecting intermittent claudication. Bicycle tests can potentially be used for patients unable to perform a treadmill test.

Test-retest reliability of the FitMáx©-questionnaire in a clinical and healthy population.

PURPOSE: The FitMáx© was developed as a questionnaire-based instrument to estimate Cardiorespiratory Fitness (CRF) expressed as oxygen uptake at peak exercise (VO2peak). Test-retest reliability is a clinometric measurement property, which defines stability over time if multiple measurements are performed (i.e. reliability). The present study aimed to assess the test-retest reliability of the FitMáx©-questionnaire in different patient groups. PATIENTS AND METHODS: A total of 127 cardiac, pulmonary and oncology patients and healthy subjects aged 19-84 years who completed the questionnaire twice within an average of 18 days were included for analysis. Participants were in a stable clinical situation (no acute disease or participating in a training program). To determine the test-retest reliability, the Intraclass Correlation Coefficient (ICC) and Standard Error of the Measurement (SEM) was calculated between the first (T0) and second (T1) administration of the questionnaires. RESULTS: An excellent agreement was found between the FitMáx©-questionnaire scores at T0 and T1, with an ICC of 0.97 (SEM 1.91) in the total study population and an ICC ranging from 0.93 to 0.98 (SEM 1.52-2.27) in the individual patient groups. CONCLUSION: The FitMáx©-questionnaire proves to be reliable and stable over time to estimate CRF of patients and healthy subjects. Trial registration NTR (Netherlands Trial Register), NL8846. Registered 25 August 2020, https://trialsearch.who.int/Trial2.aspx?TrialID=NL8846.

Monitoring aerobic capacity in cancer survivors using self-reported questionnaires: criterion validity and responsiveness.

BACKGROUND: Evaluating the criterion validity and responsiveness of the self-reported FitMáx©-questionnaire, Duke Activity Status Index (DASI) and Veterans Specific Activity Questionnaire (VSAQ) to monitor aerobic capacity in cancer survivors. METHODS: Cancer survivors participating in a 10-week supervised exercise program were included. The FitMáx©-questionnaire, DASI, VSAQ and a cardiopulmonary exercise test (CPET) were completed before (T0) and after (T1) the program. Intraclass correlation coefficients (ICC) were calculated between VO2peak estimated by the questionnaires (questionnaire-VO2peak) and VO2peak measured during CPET (CPET-VO2peak), at T0 to examine criterion validity, and between changes in questionnaire-VO2peak and CPET-VO2peak (ΔT0-T1) to determine responsiveness. Receiver operating characteristic (ROC) analyses were performed to examine the ability of the questionnaires to detect true improvements (≥ 6%) in CPET-VO2peak. RESULTS: Seventy participants were included. Outcomes at T1 were available for 58 participants (83%). Mean CPET-VO2peak significantly improved at T1 (Δ1.6 mL·kg- 1·min- 1 or 8%). Agreement between questionnaire-VO2peak and CPET-VO2peak at T0 was moderate for the FitMáx©-questionnaire (ICC = 0.69) and VSAQ (ICC = 0.53), and poor for DASI (ICC = 0.36). Poor agreement was found between ΔCPET-VO2peak and Δquestionnaire-VO2peak for all questionnaires (ICC 0.43, 0.19 and 0.18 for the FitMáx©-questionnaire, VSAQ and DASI, respectively). ROC analysis showed that the FitMáx©-questionnaire was able to detect improvements in CPET-VO2peak (area under the curve, AUC = 0.77), when using a cut-off value of 1.0 mL·kg- 1·min- 1, while VSAQ (AUC = 0.66) and DASI (AUC = 0.64) could not. CONCLUSION: The self-reported FitMáx©-questionnaire has sufficient validity to estimate aerobic capacity in cancer survivors at group level. The responsiveness of the FitMáx©-questionnaire for absolute change is limited, but the questionnaire is able to detect whether aerobic capacity improved. The FitMáx©-questionnaire showed substantial better values of validity and responsiveness compared to DASI and VSAQ.

Multimodal prehabilitation in patients with non-small cell lung cancer undergoing anatomical resection: protocol of a non-randomised feasibility study.

BACKGROUND: The preoperative period can be used to enhance a patient's functional capacity with multimodal prehabilitation and consequently improve and fasten postoperative recovery. Especially, non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is challenging, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to NSCLC surgery and aimed to conduct a study to assess feasibility and indicative evidence of efficacy of this programme. Publication of this protocol may help other healthcare facilities to implement such a programme. METHODS: The multimodal prehabilitation programme consists of an exercise programme, nutritional support, psychological support, smoking cessation, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme, and 20 will be assessed in the control group, according to patient preference. Assessments will take place at four time points: baseline, the week before surgery, 6 weeks postoperatively and 3 months postoperatively. Feasibility and indicative evidence of efficacy of the prehabilitation programme will be assessed as primary outcomes. DISCUSSION: Since the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible, and evidence of efficacy can be found. The non-randomised fashion of the study might result in a selection and confounding bias. However, the control group may help putting the results of the prehabilitation group in perspective. By publishing this protocol, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical NSCLC patients. TRIAL REGISTRATION: The current study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080 . Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.

Alpe d'HuZes cancer rehabilitation (A-CaRe) research: four randomized controlled exercise trials and economic evaluations in cancer patients and survivors.

BACKGROUND: Previous studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life. However, many previous studies had methodological weaknesses related to trial design, sample size, comparison group, outcome measures, short follow-up durations and programme content. PURPOSE: This paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d'HuZes Cancer Rehabilitation (A-CaRe) programme. METHOD: A-CaRe Clinical Research includes four randomized controlled trials in patients: (a) after chemotherapy, (b) during chemotherapy, (c) after stem cell transplantation and (d) during childhood cancer. These trials compare high-intensity resistance and endurance exercise interventions with usual care or a waiting list control group. In two studies, a second intervention arm consisting of low-to-moderate intensity exercise is included. All four A-CaRe trials use similar methods. RESULTS: Outcome measures are carefully chosen based on the International Classification of Functioning Disability and Health model. Measurements will be performed prior to randomization (T0), after completion of the intervention (T1) and at follow-up (T2). The primary outcome measures are cardiorespiratory fitness, muscle strength and fatigue. Secondary outcome measures include health-related quality of life and psychosocial functioning. Furthermore, cost-effectiveness and cost-utility analyses are performed from a societal perspective. CONCLUSION: We hypothesize that exercise is more effective at improving physical fitness and thereby reducing fatigue and more cost-effective compared with usual care or a waiting list control group. If so, the programmes will be implemented in the Dutch clinical practice.

Rehabilitation using high-intensity physical training and long-term return-to-work in cancer survivors.

INTRODUCTION: Due to large and increasing numbers of cancer survivors, long-term cancer-related health issues have become a major focus of attention. This study examined the relation between a high-intensity physical rehabilitation program and return-to-work in cancer survivors who had received chemotherapy. METHODS: The intervention group, consisting of 72 cancer survivors from one hospital (8 men and 64 women, mean age 49 years), followed an 18-weeks rehabilitation program including strength and interval training, and home-based activities. An age-matched control group, consisting of 38 cancer survivors (9 men and 29 women), was recruited from two other hospitals. They received only standard medical care. All subjects were evaluated during a telephone interview on employment issues, conducted at ±3 years after diagnosis. The main outcomes were change in working hours per week and time until return-to-work. RESULTS: Patients in the intervention group showed significant less reduction in working hours per week [-5.0 h/week vs. -10.8 h/week (P = .03)]. Multivariate analyses showed that the training intervention, the age of patients, and the number of working hours pre-diagnosis could explain the improvement in long-term participation at work. Time until (partial) return-to-work was 11.5 weeks for the intervention group versus 13.2 weeks for the control group (P = .40). On long-term follow-up, 78% of the participants from the intervention group versus 66% from the control group had returned to work on the pre-diagnosis level of working hours (P = .18). CONCLUSION: Rehabilitation using high-intensity physical training is useful for working patients to minimize the decreased ability to work resulting from cancer and its treatment.