PURPOSE:To evaluate long-term extended effects of 20 wk of high-intensity training (HIT) performed shortly after lung cancer surgery on physical fitness, muscle mass, pulmonary function, quality of life (QoL), and survival. METHODS:All participants in the original HIT-trial were invited 5 yr after surgery. Original measures were repeated by the same technician and equipment. All-cause mortality was registered 5- and 10-yr postsurgery. RESULTS:Of 61 patients who completed the 20-wk intervention, 40 (66%) were alive at 5 yr and 32 (80% of survivors; HIT n = 15, standard of care (SoC) n = 17) completed follow-up testing. No significant between-group difference was observed in the primary outcome, peak oxygen uptake 5 yr after HIT (adjusted mean difference 1.13 mL·kg -1 ·min -1 , P = 0.576). Similarly, there were no between-group differences in physical function, muscle mass, pulmonary function, or QoL. In contrast, a significant sustainable difference in leg-press strength was observed in the HIT group compared with the SoC group (23 kg, P = 0.048). Regarding survival, 5-yr survival rates were similar between the HIT group (67%) and the SoC group (65%). Although the HIT group demonstrated a tendency toward longer median postoperative survival (60.0 ± 32.6 months, 95% confidence intervals: 43.2-76.8) compared with the SoC group (43.0 ± 33.5 months, 95% confidence intervals: 24.4-61.5), this difference was not statistically significant ( P = 0.760). At 10 yr, no differences in survival rates were observed between the groups. CONCLUSIONS:Twenty weeks of HIT after lung cancer surgery led to a significant effect in leg-press strength after 5 yr but showed no long-term effects on peak oxygen uptake, muscle mass, pulmonary function, QoL, or survival compared with SoC.

Cardiorespiratory fitness (CRF) is strongly associated with morbidity and mortality in patients with Fontan circulation. However, the factors influencing CRF during adolescence remain incompletely understood. The primary aim of this study was to investigate the associations between CRF and ventricular function represented by end-diastolic pressure (VEDP), the transpulmonary pressure gradient (TPG), somatic growth (height) and pulmonary diffusing capacity (DLCO/VA). The secondary aim was to assess the prevalence of exercise oscillatory ventilation (EOV) and its physiological associations. In this national, cross-sectional study, 44 adolescents (median age 16.6 years) with Fontan circulation underwent cardiopulmonary exercise testing, heart catheterization and pulmonary function assessment. Peak oxygen uptake (V̇O₂peak) was modelled as the dependent variable in a multiple linear regression with VEDP, TPG, height, and DLCO/VA as predictors. Logistic regression was used to identify physiological associations of EOV. The multiple regression model for absolute V̇O₂peak explained 61

BACKGROUND:Fatigue is a prevalent and distressing late effect among childhood cancer survivors (CCSs), yet its physiological determinants remain unclear. This study examined the associations between physical fitness (VO2peak and muscular strength), physical function (sit-to-stand [STS] performance), physical activity, and fatigue in adolescent CCSs, and whether these associations differ from those observed in healthy controls. METHODS:This cross-sectional analysis was part of the international multicenter Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study, including CCSs and age- and sex-matched healthy controls. Fatigue was assessed using the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale. Physical fitness and function were evaluated by cardiopulmonary exercise testing (VO2peak), isometric muscular strength (knee extension, chest press, and handgrip), and the 1-min STS test. Physical activity was measured by accelerometry. Associations between physical fitness, physical activity, and fatigue were examined using multivariable mixed-effects linear regression models. RESULTS:A total of 123 CCSs (mean age 13.5 ± 2.5 years, 6.7 ± 3.5 years posttreatment) and 99 controls (mean age 13.1 ± 2.6 years) were included. Total fatigue scores among CCSs and controls were 72.6 ± 17.1 and 74.8 ± 15.7, respectively (p = 0.324). Higher VO2peak (β = 0.66, 95% confidence interval [CI] 0.14-1.17, p = 0.012) and greater muscular strength (β = 5.85, 95% CI 0.63-11.08, p = 0.028) were associated with less fatigue in CCSs, whereas activity levels were not associated with fatigue. No significant differences were observed in the association of physical fitness or physical activity measures with fatigue between CCSs and controls. CONCLUSION:Higher physical fitness, but not physical activity level, was associated with lower fatigue in adolescent CCSs, with similar associations observed in healthy controls. These findings highlight physical fitness as a potential target for fatigue management in adolescent CCSs.

INTRODUCTION:Cisplatin-based chemotherapy (CBCT) is standard treatment for most men with metastatic testicular cancer (TC). The main objective was to evaluate changes in physical fitness and body composition from before to immediately after CBCT and 3 months after completion of CBCT. PATIENTS AND MATERIALS:The assessments included cardiorespiratory fitness (peak oxygen uptake [VO2 peak]), muscle strength (1 repetition maximum [1RM]) and muscular endurance in leg- and chest press, body composition (dual-energy X-ray absorptiometry), physical activity (PA) levels, and patient-reported outcomes (functional scales, global quality of life [QoL], mental health and fatigue). Twenty-eight patients were included, most with low-volume metastatic disease and all within the good prognosis risk group. RESULTS:From before the start of CBCT to immediately after the last CBCT cycle, there were significant reductions in VO2 peak by 24% (P < .001), 1RM leg press by 8% (P = .004), 1RM chest press by 17% (P = .001), chest press endurance by 22% (P = .005), total lean body mass by 2.2 kg (P < .001), PA level, physical-, role-, cognitive- and social functioning, and QoL; and significant increases in total and physical fatigue and symptoms of depression. There was a good correlation between reductions in VO2 peak and QoL during CBCT (r = 0.54, P = .016), whereas no correlation between reductions in VO2 peak and PA levels. Twelve weeks after CBCT, all variables had returned to baseline values except for PA levels and physical functioning. CONCLUSION:TC patients should be prepared for reductions in physical fitness and QoL during CBCT. The reduction in cardiovascular fitness is possibly independent of the PA level.

OBJECTIVES:This study aimed to compare physical fitness, function, and physical activity (PA) in adolescent childhood cancer survivors (CCSs) to age- and sex-matched controls and across different cancer diagnoses. METHODS:This multicenter cross-sectional study (Physical Activity among Childhood Cancer Survivors) included CCSs aged 9-18 yr (≥1-yr after cancer treatment) and age- and sex-matched controls. Physical fitness tests included cardiorespiratory fitness (V̇O 2max ) and muscular strength (maximal isometric handgrip, knee extension, and chest press). Physical function tests included a 1-min sit-to-stand test (STS) and countermovement jump (CMJ). PA was measured by accelerometer for 7 d. We used linear mixed-effects models to compare outcomes between CCSs and controls, and across diagnostic groups. RESULTS:We included 157 CCSs and 113 controls aged 13.4 ± 2.6 yr (mean ± SD). Cancer types were leukemia ( n = 78), central nervous system (CNS) tumors ( n = 18), lymphoma ( n = 16), and other solid tumors ( n = 45). CCSs had lower V̇O 2max (marginal mean (95% confidence interval), 41.7 (38.4-45.0) vs 46.4 (42.9-49.8) mL·kg -1 ·min -1 ; P < 0.001), knee-extension strength (35.4 (34.1-36.8) vs 38.2 (36.7-39.7) kg, P = 0.003), chest-press strength (30.0 (28.4-31.6) vs 32.8 (31.0-34.7) kg, P = 0.007), STS repetitions (57.5 (55.8-59.3) vs 60.0 (58.0-62.0) P = 0.017), and CMJ height (22.1, (20.5-23.8) vs 24.9 (23.2-26.6) cm, P < 0.001). PA levels and sedentary time were similar in both groups (8513 (7993-9034) vs 9000 (8404-9596) steps per day, P = 0.174, respectively). Survivors of CNS tumors had the lowest values for V̇O 2max , muscular strength, physical function, and PA. CONCLUSIONS:Despite no significant difference in PA levels, adolescent CCSs had 4.2% to 11% lower physical fitness and function compared with controls, where survivors of CNS tumors performed the poorest.

Background Poor cardiorespiratory fitness (CRF) is associated with a higher symptom burden and an increased prevalence of long-term treatment–related cardiovascular disease risk factors in cancer survivors. However, the magnitude of systemic therapy–related CRF impairment remains unclear. Objectives The aim of this study was to evaluate the effects of systemic anticancer treatment on CRF and identify physiological determinants underpinning CRF impairment. Methods A systematic literature search was performed in PubMed, Embase, CINAHL, SPORTDiscus, and the Cochrane Library. The primary endpoint was the change in CRF, measured by peak oxygen consumption (Vo2peak), from before to after systemic treatment. Secondary endpoints included post-treatment differences in Vo2peak between cancer survivors and noncancer control subjects, along with physiological determinants of Vo2peak. Two meta-regressions were conducted to examine the association between CRF and cardiac output and arteriovenous oxygen difference. Results A total of 44 studies were included, comprising 27 prospective trials (61%; n = 1,234 cancer survivors, median age 52.4 years) and 17 cross-sectional studies (39%; n = 1,372 cancer survivors, median age 54.0 years; n = 1,923 noncancer control subjects, median age 56.0 years). Systemic anticancer treatment was associated with a significant decrease in Vo2peak (weighted mean difference −2.13 mL·kg−1·min−1; 95% CI: −2.76 to −1.50 mL·kg−1·min−1). No significant differences were observed between patient subgroups (esophagogastric, breast, and colon or rectal cancers). At a median follow-up of 2 years (range: 6 weeks to 12 years) post-therapy, cancer survivors had a significantly lower Vo2peak (weighted mean difference −6.39 mL·kg−1·min−1; 95% CI: −7.60 to −5.18 mL·kg−1·min−1) compared with noncancer control subjects. Reduced arteriovenous oxygen difference was associated with lower Vo2peak (β = 2.55; 95% CI: 2.05-3.06; P < 0.001). Conclusions Systemic anticancer treatment leads to substantial and sustained impairments in CRF.

BACKGROUND:Cancer treatment may impair physiological adaptations to exercise therapy, yet no study has directly compared exercise effects between cancer survivors and cancer-naive control subjects. OBJECTIVES:This study sought to examine the effects of aerobic exercise in anthracycline-treated long-term survivors of breast cancer (BCS) and to compare the effects to cancer-naive women. METHODS:The CAUSE (CArdiovascUlar Survivors Exercise) trial was a 2-arm randomized controlled trial in which long-term BCS were assigned to thrice-weekly nonlinear aerobic exercise for 5 months (BCS exercise) or usual care (BCS usual care). A third group of similarly aged cancer-naive women completed the same exercise intervention. The primary outcome was cardiorespiratory fitness (CRF) (measured as Vo2peak). Secondary outcomes included cardiovascular risk factors (cardiometabolic biomarkers and body composition) and patient-reported outcomes (subjective vitality and life satisfaction). RESULTS:Between October 2020 and February 2023, 140 BCS (aged 59.0 ± 6.4 years; 11 ± 1 years after treatment) and 69 cancer-naive women (aged 57.8 ± 4.9 years) were enrolled. From baseline to post-exercise intervention, Vo2peak increased by 1.2 ± 2.6 mL·kg-1·min-1 in the BCS exercise, by 0.01 ± 2.5 mL·kg-1·min-1 in the BCS usual care group (mean difference 1.3; 95% confidence interval [CI]: 0.5-2.1; P = 0.002), and by 2.6 ± 2.5 mL·kg-1·min-1 in non-cancer subjects (BCS exercise vs non-cancer subjects: mean difference -1.4; 95% CI: -2.2 to -0.5; P = 0.003). No changes in cardiovascular risk factors were observed. Compared with BCS usual care, the BCS exercise group reported improved subjective vitality (mean difference 2.56; 95% CI: 1.22-3.90; P < 0.001) and satisfaction with life (mean difference 1.68; 95% CI: 0.43-2.93; P = 0.009). CONCLUSIONS:Although aerobic exercise improves CRF in anthracycline-treated long-term BCS, the response was less than one-half that observed in cancer-naive subjects.

Cancer treatment may impair the physiological adaptations to exercise training according to earlier exercise training trials. Nonetheless, reduced exercise training response has not been systematically studied in cancer survivors. To examine the effects of aerobic exercise on cardiorespiratory fitness (CRF) and cardiovascular (CV) risk factors in anthracycline-treated long-term breast cancer survivors (BCSs) and compared these effects with women without cancer following the same exercise program. The CAUSE (CArdiovascUlar Survivors Exercise) trial was a two-armed randomized controlled trial, where long-term BCSs were assigned to five months of aerobic exercise training 3 times per week or to usual care. Similar-aged women without cancer underwent the same exercise program. CRF was assessed as peak oxygen consumption (V̇O2peak), and CV risk factors including cardiometabolic biomarkers and body composition were assessed at baseline and post-intervention. Patient-reported outcomes were assessed using the Subjective Vitality Scale (SVS) and the Satisfaction With Life Scale (SWLS). We included, 140 BCSs (aged 59.0±6.4 years), 11±1 years post-treatment, and 69 women without cancer (aged 57.8±4.9 years) between October 2020 and February 2023. Intervention adherence and loss to follow-up were similar between the exercise groups. VO2peak increased by 1.22±2.63 mL O2×kg-1×min-1 in BCSs after exercise training from baseline to post-intervention, 0.02±2.47 mL O2×kg-1×min-1 in BCSs after usual care [mean difference 1.32 (95% CI: 0.501; 2148), p=0.002] and 2.64±2.51mL in women without cancer after exercise training [BCSs exercise training VS. women without cancer: Mean difference -1.41, (95% CI: -2.267; -0.545), p=0.002]. There were no significant changes in CV risk factors from baseline to post-intervention between the groups. SVS [mean difference 2.56, (95% CI: 1.215; 3.897), p=<0.001] and SWLS [mean difference 1.68, (95% CI: 0.428; 2.932), p=0.009) significantly improved in BCSs after exercise training compared to BCSs after usual care, with greater changes in SWLS in BCSs after exercise training compared to women without cancer [mean difference 1.71, (95% CI: 0.262; 2.157), p=0.021]. A decade after anthracycline treatment, aerobic exercise training improves CRF in long-term BCSs. Importantly, however, the exercise training response was lower in BCSs compared to women without cancer.

Objective:To evaluate exercise testing (ExT) characteristics, safety, and methodological quality in oncology settings. Patients and Methods:In this systematic review, we searched electronic databases (PubMed, Embase, CINAHL, and Cochrane Library) from inception to March 2024. Studies using ExT to evaluate cardiorespiratory fitness or functional capacity in adults with a history of cancer were included. Summary data including ExT characteristics (eg, modality, cardiorespiratory fitness, and functional capacity results), safety (eg, adverse events [AE]), and methodological quality (eg, guideline adherence) was evaluated. Results:A total of 642 unique studies with 94,960 patients (58.6±9.9 years; 49% women) were included. Among the 26 ExT modalities used, the maximal cardiopulmonary exercise test (CPET) with measurement of gas exchange (n=284, 40%) and the 6-minute walk test (6MWT) (n=240, 34%) were the most frequently performed. Of the 284 studies that conducted CPET, n=204 (72%) studies reported peak oxygen consumption in mL·kg-1·min-1; average peak oxygen consumption was 21.8±5.8 mL·kg-1·min-1. Of the 237 studies that conducted 6MWT, 155 (65%) reported distance in meters (m); average distance was 445m±79 m. A total of n=36 (23%) studies reported an average distance above 500 meter. The AEs were monitored in 58 (9.0%) studies wherein a total of 120 non-serious AEs were reported among n=5699 patients (0.02%). Methodological quality and reporting varied considerably. Conclusion:The findings of this systematic review indicate that CPET with gas exchange and field-based tests such as the 6MWT are widely used; however, future research should prioritize improving safety monitoring, appropriate test selection, and methodological consistency to enhance the applicability of ExT in oncology care.

Cardiopulmonary Exercise Testing (CPET) is considered the gold standard assessment of peak oxygen uptake ( $$\dot VO_2$$ V ˙ O 2 peak), and consequently, cardiorespiratory fitness (CRF). Common practice in children with congenital heart diseases (CHD) is to compare individual test results to reference values in healthy children. This approach does not account for the diversity of heart defects and may also be demotivating for children with CHD. This retrospective multicentre study aimed to establish individualized CRF reference models specific to children with CHD, to facilitate a better understanding and management of their condition. A total of 1475 CPETs until exhaustion were performed in 943 children and adolescents at two hospitals in Norway. The children and adolescents were categorized into three groups: simple defects (VSD, ASD, CoA, LVOTO; n = 497, 38% female), moderate defects (TGA, Fallot; n = 299, 41% female), and univentricular defects with a Fontan circulation ( n = 147, 42% female). Multivariable mixed-effects models with individuals as random intercepts were used to develop group-specific reference models for CRF. Estimated predictive models including covariance matrices for each group and outcome are provided, allowing for the generation of reference values with confidence intervals for clinical and research applications. Conclusion: Treadmill-based reference models for maximal and submaximal CRF variables in the most prevalent types of CHD are presented. Using individualized reference values has the potential to improve clinical decision-making for children with CHD and to enhance their sense of mastery. A web-based calculator is available for quick and easy clinical use. What is Known: • Children with congenital heart disease (CHD) generally have reduced cardiorespiratory fitness (CRF) compared to healthy peers. Treadmill-based reference values for CRF in CHD are limited. What is New: • This study provides individualized, treadmill-based reference models for maximal and submaximal CRF variables in children with various CHD. • A web-based calculator is available for quick and easy clinical use. • This approach may improve the interpretation of CRF in children with CHD. Graphical abstract Graphical abstract: Created in BioRender. Klungerbo, V. (2025) https://BioRender.com/w93q182 .

OBJECTIVES:The objectives of the present study were 1) to describe changes in fatigue from 3 to 12 months post-stroke and compare different patterns of fatigue changes with respect to concurrent changes in physical fitness, body composition, and activity levels, and 2) to explore whether changes in fatigue are associated with changes in physical fitness, body composition, and physical activity levels in patients recovering from first-ever ischemic stroke. MATERIALS AND METHODS:In this longitudinal observational study, we assessed 72 patients (mean age 62 years, 36 % females) at 3 and 12 months after first-ever ischemic stroke. Fatigue was measured with the 7-item Fatigue Severity Scale. Physical fitness, body composition and physical activity were assessed using cardiopulmonary exercise testing, physical function tests, Dual-energy X-ray Absorptiometry, and accelerometers. RESULTS:Fatigue levels was stable between 3 and 12 months post-stroke in 44 (61 %) patients, decreased in 14 (19 %), and increased in another 14 (19 %). Patients with increased fatigue levels showed a greater decrease in cardiorespiratory fitness, as measured directly by peak oxygen uptake, compared to those with decreased fatigue. Robust regression analysis, adjusted for age and sex, indicated that each kilogram of lean body mass gained from 3 to 12 months post-stroke was significantly associated with a 0.3-point reduction in fatigue during the same timeframe (B= -0.32; 95 %CI [-0.51, -0.12]). CONCLUSION:There was considerable individual variation in changes to fatigue, physical fitness, body composition, and physical activity levels between 3 and 12 months following a first-ever ischemic stroke. Increased fatigue was linked to a greater concurrent decline in cardiorespiratory fitness, while lean body mass was associated with decreases in fatigue.

BACKGROUND:Chronic fatigue (CF) is a highly disabling late effect after cancer, affecting 25% to 40% of lymphoma survivors years after cancer treatment. There is a lack of randomized controlled trials testing interventions to reduce fatigue levels among survivors with CF. OBJECTIVE:The primary aim of the Randomized Controlled Trial in Chronically Fatigued Lymphoma Survivors (REFUEL) is to examine the effects of a multidisciplinary intervention on the level of fatigue among lymphoma survivors with CF before and immediately after the intervention (3 months after randomization). Secondary aims are to (1) investigate the effects of the intervention on the level of fatigue 6 and 9 months after randomization and the effects on health-related quality of life (HRQoL); other patient-reported outcome measures; and physical fitness 3, 6, and 9 months after randomization; (2) evaluate the cost-utility of the intervention; (3) examine the effect of the intervention on HRQoL among the survivors' partners; and (4) investigate the long-term perceived benefits and daily use of acquired self-management strategies, as well as measure changes in fatigue, daily functioning, HRQoL, mental health, and work-life balance management within each group at 1- and 2-year follow-ups. METHODS:The REFUEL trial is a 2-armed randomized controlled trial. Lymphoma survivors (2-12 years after diagnosis) with CF are randomly allocated to a 12-week multidisciplinary intervention including patient education, physical exercise, a cognitive behavioral therapy-based group program, and individual nutrition counseling or to usual care. Fatigue is measured by the Chalder Fatigue Questionnaire. Other patient-reported outcome measures are measured by validated questionnaires (eg, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire, the Patient Health Questionnaire-9, and the Generalized Anxiety Disorder-7). Cardiorespiratory fitness is measured as peak oxygen consumption during a cardiopulmonary exercise test or indirectly using a modified Balke treadmill protocol. Muscle strength is assessed by push-ups and leg press. The primary analyses will be performed using a generalized linear mixed model for repeated measures, with an intention-to-treat approach. RESULTS:A total of 150 survivors were included from December 2021 to March 2023. Three-month postrandomization assessments were completed in June 2023 and 2-year follow-up assessments were completed in June 2025. CONCLUSIONS:The REFUEL trial will provide new and highly needed scientific evidence about the effects of a multidisciplinary intervention on the level of fatigue and secondary outcomes regarding HRQoL aspects among lymphoma survivors with CF. TRIAL REGISTRATION:ClinicalTrials.gov NCT05130099; https://www.clinicaltrials.gov/study/NCT05130099. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/69336.

BACKGROUND:Breast cancer survivors (BCSs) are at increased risk of late effects. While research has reported positive effects of exercise therapy on fatigue and health-related quality of life (HRQoL) among short-term BCSs, evidence in long-term survivors remains scarce. METHODS:The CAUSE (CArdiovascUlar Survivors Exercise) trial was a 2-armed randomized controlled trial. Long-term BCSs were assigned to 5 months of thrice-weekly supervised aerobic exercise or usual care. Late effects and HRQoL were assessed by Chalder Fatigue Questionnaire, European Organization for Research and Treatment of Cancer QLQ-BR23 and QLQ-C30 questionnaires, and Scale for Chemotherapy-Induced Long-term Neurotoxicity at baseline (T0), post-intervention (T1), and 1-year follow-up (T2). RESULTS:In total, 140 BCSs (mean age 59.0 ± 6.4 years, 11 ± 1 years post-treatment) were included. Loss to follow-up at T1 was 6% and 19% in the exercise- and usual care group, respectively. From T0 to T1, the exercise group significantly improved total fatigue (between groups mean difference [MD] = -3.0, P < .001), body image (MD = 6.7, P = .043), physical- (MD = 3.2, P ≤ .001), role- (MD = 9.6, P = .019), and cognitive function (MD = 3.4, P = .038), insomnia (MD = -9.0, P = .017), and global health/QoL (MD = 5.3, P ≤ .001) compared to usual care. The exercise benefits were more pronounced in BCSs experiencing versus not experiencing late effects at baseline. At 1-year follow-up, most improvements regressed toward baseline values. CONCLUSION:Aerobic exercise significantly improves fatigue, body image, physical-, role-, and cognitive function, insomnia, and HRQoL in long-term BCSs. These findings suggest that exercise therapy should be a core component of managing late effects and enhancing HRQoL in long-term BCSs. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov/. Registration number: NCT04307407.

Poor cardiorespiratory fitness (CRF) is associated with a higher symptom burden and an increased prevalence of long-term treatment-related cardiovascular disease risk factors in cancer survivors. However, the magnitude of systemic therapy-related CRF impairment remains unclear. The aim of this study was to evaluate the effects of systemic anticancer treatment on CRF and identify physiological determinants underpinning CRF impairment. A systematic literature search was performed in PubMed, Embase, CINAHL, SPORTDiscus, and the Cochrane Library. The primary endpoint was the change in CRF, measured by peak oxygen consumption (Vo2peak), from before to after systemic treatment. Secondary endpoints included post-treatment differences in Vo2peak between cancer survivors and noncancer control subjects, along with physiological determinants of Vo2peak. Two meta-regressions were conducted to examine the association between CRF and cardiac output and arteriovenous oxygen difference. A total of 44 studies were included, comprising 27 prospective trials (61%; n = 1,234 cancer survivors, median age 52.4 years) and 17 cross-sectional studies (39%; n = 1,372 cancer survivors, median age 54.0 years; n = 1,923 noncancer control subjects, median age 56.0 years). Systemic anticancer treatment was associated with a significant decrease in Vo2peak (weighted mean difference -2.13 mL·kg-1·min-1; 95% CI: -2.76 to -1.50 mL·kg-1·min-1). No significant differences were observed between patient subgroups (esophagogastric, breast, and colon or rectal cancers). At a median follow-up of 2 years (range: 6 weeks to 12 years) post-therapy, cancer survivors had a significantly lower Vo2peak (weighted mean difference -6.39 mL·kg-1·min-1; 95% CI: -7.60 to -5.18 mL·kg-1·min-1) compared with noncancer control subjects. Reduced arteriovenous oxygen difference was associated with lower Vo2peak (β = 2.55; 95% CI: 2.05-3.06; P < 0.001). Systemic anticancer treatment leads to substantial and sustained impairments in CRF.

PURPOSE The magnitude of cardiorespiratory fitness (CRF) impairment during anticancer treatment and CRF response to aerobic exercise training (AT) are highly variable. The aim of this ancillary analysis was to leverage machine learning approaches to identify patients at high risk of impaired CRF and poor CRF response to AT. METHODS We evaluated heterogeneity in CRF among 64 women with metastatic breast cancer randomly assigned to 12 weeks of highly structured AT (n = 33) or control (n = 31). Unsupervised hierarchical cluster analyses were used to identify representative variables from multidimensional prerandomization (baseline) data, and to categorize patients into mutually exclusive subgroups (ie, phenogroups). Logistic and linear regression evaluated the association between phenogroups and impaired CRF (ie, ≤16 mL O2·kg–1·min–1) and CRF response. RESULTS Baseline CRF ranged from 10.2 to 38.8 mL O2·kg–1·min–1; CRF response ranged from –15.7 to 4.1 mL O2·kg–1·min–1. Of the n = 120 candidate baseline variables, n = 32 representative variables were identified. Patients were categorized into two phenogroups. Compared with phenogroup 1 (n = 27), phenogroup 2 (n = 37) contained a higher number of patients with none or >three lines of previous anticancer therapy for metastatic disease and had lower resting left ventricular systolic and diastolic function, cardiac output reserve, hematocrit, lymphocyte count, patient-reported outcomes, and CRF ( P < .05) at baseline. Among patients allocated to AT (phenogroup 1, n = 12; 44%; phenogroup 2, n = 21; 57%), CRF response (–1.94 ± 3.80 mL O2·kg–1·min–1 v 0.70 ± 2.22 mL O2·kg–1·min–1) was blunted in phenogroup 2 compared with phenogroup 1. CONCLUSION Phenotypic clustering identified two subgroups with unique baseline characteristics and CRF outcomes. The identification of CRF phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions among patients with cancer.

Background: Research on cardiorespiratory fitness (CRF) in relation to physical activity (PA) and fatigue after stroke is limited. Increased knowledge of interrelationships between these factors can help optimize rehabilitation strategies and improve health-outcomes. Objectives: We aimed to: 1) evaluate CRF, PA, and fatigue, 2) characterize patients with impaired versus non-impaired CRF, and 3) examine associations of CRF with PA and fatigue, three months after first-ever ischemic stroke. Methods: In this cross-sectional study CRF was measured as peak oxygen uptake (VO2peak) by cardiopulmonary exercise testing. PA was measured using accelerometers. Fatigue was assessed with the 7-item Fatigue Severity Scale (FSS). Results: The sample (n=74, mean age 64 +/- 13 years, 36% women) had a mean VO2peak of 27.0 +/- 8.7 (86% of predicted). Fifty-one percent met the World Health Organization's recommendation of >= 150 min of moderate PA/week. Mean steps-per-day was 9316 +/- 4424 (113% of predicted). Thirty-five percent of the sample had moderate-to-high fatigue (FSS >= 4), mean FSS score was 3.2 +/- 1.8. Patients with impaired CRF (VO2peak<80% of predicted) had higher body-fat-percent (p<0.01), less moderate-to-vigorous PA (MVPA) (p<0.01) and a trend toward higher fatigue (p=0.053) compared to the non-impaired. Backward regression analysis showed that higher CRF was associated with more MVPA (unstandardized beta [95% CI]: 0.38 [0.15, 0.63], p=0.002) and less fatigue (unstandardized beta [95% CI]: -3.9 [-6.4, -1.6], p=0.004). Conclusions: Stroke patients had lower CRF compared to reference values. Impaired CRF was mainly related to overweight. Higher CRF was associated with more MVPA and less fatigue. Exercise after stroke may be especially beneficial for patients with impaired CRF.

Chronic fatigue (CF) is a highly disabling late effect after cancer, affecting 25-40% of lymphoma survivors years after cancer treatment. There is a lack of randomized controlled trials (RCTs) testing interventions to reduce fatigue levels among survivors with CF. The primary aim of the randomized controlled REFUEL-trial is to examine the effects of an interdisciplinary intervention on the level of fatigue among lymphoma survivors with CF from pre- to immediately post-intervention. Secondary aims are to 1) investigate the effects of the intervention on level of fatigue three and six months post-intervention, and the effects on health-related quality of life (HRQoL), other patient-reported outcomes and physical fitness immediately, three and six months post-intervention, 2) evaluate the cost-utility of the intervention, 3) examine the effect of the intervention on HRQoL among the survivors’ partners and 4) investigate the long-term perceived benefits and daily use of acquired self-management strategies, as well as changes in fatigue, daily functioning, HRQoL, mental health, and work-life within each group at 12 and 24 months post-intervention. The REFUEL-trial is a two-armed RCT. Lymphoma survivors (2-12 years post-diagnosis) with CF are randomly allocated to a 12-week interdisciplinary intervention including patient education, physical exercise, a cognitive behavioral therapy-based group program and individual nutrition counselling, or to usual care. Fatigue is measured by the Chalder Fatigue Questionnaire. Other patient-reported outcomes are measured by validated questionnaires (e.g. European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7)). Cardiorespiratory fitness is measured as peak oxygen consumption (VO2peak) during a cardiopulmonary exercise test, or indirectly using a modified Balke treadmill protocol. Muscle strength is assessed by push-ups and leg press. A total of 150 survivors were included from December 2021 to March 2023. Post-intervention assessments were completed in June 2023, and 24 months follow-up will be completed in June 2025. The REFUEL-trial will provide new and highly needed scientific evidence about the effects of an interdisciplinary intervention for lymphoma survivors with CF, their partners, and cost-utility for society. The study is preregistered on clinicaltrials.gov (NCT05130099).

BACKGROUND:Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown.OBJECTIVE:The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes.METHODS:The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO2peak), limiting factors for VO2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention.RESULTS:A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025.CONCLUSIONS:The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors.TRIAL REGISTRATION:ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/45244.