Incorporating Exercise Training into Cardio-Oncology Care: Current Evidence and Opportunities: JACC: CardioOncology State-of-the-Art Review.

Cancer treatment-induced cardiotoxicities are an ongoing concern throughout the cancer care continuum from treatment initiation to survivorship. Several "standard-of-care" primary, secondary, and tertiary prevention strategies are available to prevent the development or further progression of cancer treatment-induced cardiotoxicities and their risk factors. Despite exercise's established benefits on the cardiovascular system, it has not been widely adopted as a nonpharmacologic cardioprotective strategy within cardio-oncology care. In this state-of-the-art review, the authors discuss cancer treatment-induced cardiotoxicities, review the existing evidence supporting the role of exercise in preventing and managing these sequelae in at-risk and affected individuals living after cancer diagnoses, and propose considerations for implementing exercise-based services in cardio-oncology practice.

Physical activity and physical fitness assessments in adolescents and young adults diagnosed with cancer: a scoping review.

PURPOSE: This scoping review describes the assessment methodologies for physical activity (PA) and physical fitness assessments used in studies focusing on adolescents and young adults (AYAs) diagnosed with cancer. METHODS: A search of the literature was conducted in PubMed, CINAHL, Web of Science, and Cochrane Library following the PRISMA-ScR statement. A total of 34 studies were included in this review. RESULTS: PA was primarily assessed via self-reported questionnaires (30/34) either completed in-person (n = 17) or online (n = 13) at different time points and different stages along the cancer trajectory (i.e., from diagnosis onward). A total of 9 studies conducted a physical fitness assessment. CONCLUSIONS: PA and physical fitness measurements are key when trying to describe outcomes, assess for associations, track changes, measure intervention adherence, and test intervention efficacy and effectiveness. Considerable heterogeneity across studies was reported limiting the generation of formal recommendations or guidance for researchers, healthcare providers, and policy makers.

Self-Reported Physical Activity, QoL, Cardiac Function, and Cardiorespiratory Fitness in Women With HER2+ Breast Cancer.

Background: Women treated for breast cancer are at risk for worsening health-related quality of life (QoL), cardiac function, and cardiorespiratory fitness. Objectives: The aim of this study was to assess the associations of self-reported moderate to vigorous intensity physical activity (MVPA) during cancer treatment with concurrent measures of QoL and cardiac function and with post-treatment cardiorespiratory fitness in women with human epidermal growth factor receptor 2-positive breast cancer receiving sequential anthracyclines and trastuzumab. Methods: EMBRACE-MRI 1 (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI) study participants who completed questionnaires for MVPA (modified Godin Leisure Time Physical Activity Questionnaire) and QoL (EQ-5D-3L, Minnesota Living With Heart Failure Questionnaire) and cardiac imaging every 3 months during treatment and post-treatment cardiopulmonary exercise testing were included. Participants engaging in ≥90 minutes of MVPA each week were labeled "active." Generalized estimation equations and linear regression analyses were used to assess concurrent and post-treatment associations with MVPA and activity status, respectively. Results: Eighty-eight participants were included (mean age 51.4 ± 8.9 years). Mean MVPA minutes, QoL, and cardiac function (left ventricular ejection fraction, global longitudinal strain, E/A ratio, and E/e' ratio) worsened by 6 months into trastuzumab therapy. Higher MVPA (per 30 minutes) during treatment was associated with better concurrent overall (ß = -0.42) and physical (ß = -0.24) Minnesota Living With Heart Failure Questionnaire scores, EQ-5D-3L index (ß = 0.003), visual analogue scale score (ß = 0.43), diastolic function (E/A ratio; ß = 0.01), and global longitudinal strain (ß = 0.04) at each time point (P ≤ 0.01 for all). Greater cumulative MVPA over the treatment period was associated with higher post-treatment cardiorespiratory fitness (peak oxygen consumption; ß = 0.06 per 30 minutes; P < 0.001). Conclusions: Higher self-reported MVPA during treatment for human epidermal growth factor receptor 2-positive breast cancer was associated with better QoL and diastolic and systolic left ventricular function measures during treatment and better post-treatment cardiorespiratory fitness.

Research Quality and Impact of Cardiac Rehabilitation in Cancer Survivors: A Systematic Review and Meta-Analysis.

Background: Cardiac rehabilitation (CR) is endorsed to improve cardiovascular outcomes in cancer survivors. The quality of CR-based research in oncology has not been assessed. Objectives: The aim of this study was to evaluate the quality of reporting and evidence from CR-based intervention studies in oncology and to explore associations between intervention participation and outcomes. Methods: Systematic searches of 5 databases were conducted (January 2020) and updated (September 2021). Randomized and nonrandomized studies evaluating CR-based interventions in adult cancer survivors during and after treatment were eligible. Independent reviewers extracted data using 2 reporting guidelines (Template for Intervention Description and Replication and Consolidated Standards for Reporting Trials Harms extension), risk of bias (ROB) assessment tools (Cochrane ROB 2.0 and Cochrane Risk of Bias in Non-Randomized Studies of Interventions), and a combined inventory (Tool for the Assessment of Study Quality and reporting in Exercise). A meta-analysis was used to explore pre-intervention/post-intervention differences for commonly assessed outcomes. Results: Ten studies involving data from 685 survivors were included. The mean quality scores for intervention reporting (Template for Intervention Description and Replication) and harms (Consolidated Standards for Reporting Trials Harms extension) were 62% and 17%, respectively. There was moderate-to-high ROB across nonrandomized (Cochrane Risk of Bias in Non-Randomized Studies of Interventions score: 25%) and randomized (ROB 2.0 score: 50%) studies. The mean standardized cardiorespiratory fitness was higher (0.42; 95% CI: 0.27-0.57), fatigue was lower (-0.45; 95% CI: -0.55 to -0.34), and percent body fat (0.07; 95% CI: -0.23 to 0.38) was not different in survivors completing CR compared with those not completing CR. Conclusions: CR-based studies in oncology have low-to-moderate reporting quality and moderate-to-high ROB limiting interpretation, reproducibility, and translation of this evidence into practice.

Exercise and Rehabilitation in People With Ehlers-Danlos Syndrome: A Systematic Review.

Objective: To conduct a systematic review examining the effect of exercise and rehabilitation in people with Ehlers-Danlos syndrome (EDS). Data Sources: The following databases were systematically searched: MEDLINE, MEDLINE In-Process/ePubs, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Cumulative Index to Nursing and Allied Health. The final time point captured by the search is November 27, 2020. Study Selection: Eligible study designs included case-control, case-series, prospective cohort, retrospective cohort, and intervention studies of structured exercise or rehabilitation interventions. Eligible populations included adults (18 years or older) with EDS (all subtypes) and hypermobility spectrum disorders. The search was restricted to articles published in English. Data Extraction: Data were extracted by 2 independent reviewers. Risk of bias was assessed using the Physiotherapy Evidence Database (PEDro) scale for randomized controlled trials (RCTs) and Risk Of Bias In Nonrandomized Studies of Interventions (ROBINS-I) for non-RCTs. Reporting quality of RCTs was assessed using the Consolidated Standards for Reporting of Trials statement with the harms extension. Reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data Synthesis: The search yielded 10 eligible studies including 330 participants. The study designs included 5 RCTs, 1 cohort, 2 single-arm interventions, 1 retrospective, and 1 feasibility study. All studies showed some improvement in a physical and/or psychological outcome after the intervention period. One adverse event (nonserious) potentially related to the intervention was reported. Of the 5 RCTs, 2 were rated as high quality with low risk of bias using PEDro, and the majority of non-RCTs were rated as critical risk of bias by ROBINS-I. Conclusions: The results suggest that exercise and rehabilitation may be beneficial for various physical and psychological outcomes. Adequately powered and rigorous RCTs of exercise and rehabilitation interventions for people with EDS are needed.

Testing of a Self-administered 6-Minute Walk Test Using Technology: Usability, Reliability and Validity Study.

BACKGROUND: The need to attend a medically supervised hospital- or clinic-based appointment is a well-recognized barrier to exercise participation. The development of reliable and accurate home-based functional tests has the potential to decrease the burden on the health care system while enabling support, information, and assessment. OBJECTIVE: This study aims to explore the usability (ie, acceptability, satisfaction, accuracy, and practicality) of the EasyMeasure app to self-administer the 6-minute walk test (6MWT) in young, healthy adults and determine parallel form reliability and construct validity of conducting a self-administered 6MWT using technology. METHODS: We used a usability study design. English-speaking, undergraduate university students who had access to an iPhone or iPad device running iOS 10 or later and self-reported ability to walk for 6 minutes were recruited for this study. Consenting participants were randomized to either a standard 6MWT group (ie, supervised without the use of the app) or a technology 6MWT group (ie, unsupervised with the app to mimic independent implementation of the test). All participants performed a maximal treadmill test. Participants in the 6MWT group completed the Unified Theory of Acceptance and Use of Technology (UTAUT) questionnaire and a satisfaction questionnaire after completing the assessment. Parallel form reliability of the 6MWT using technology was analyzed by comparing participant self-administered scores and assessor scores using Pearson correlation coefficients across and between trials. Construct validity was assessed by comparing participant 6MWT scores (both standard and using technology) with maximum treadmill test variables (peak oxygen uptake and ventilatory threshold [VT]). RESULTS: In total, 20 university students consented to participate in the study. All but 2 participants (8/10, 80%) in the technology 6MWT group had deviations that prevented them from accurately conducting the 6MWT using the app, and none of the participants were able to successfully score the 6MWT. However, a significantly strong correlation was found (r=.834; P=.003) when comparing participants' scores for the 6MWT using technology with the assessors' scores. No significant correlations were found between maximal treadmill test peak oxygen uptake scores and 6MWT prediction equations using standard 6MWT scores (equation 1: r=0.119; P=.78; equation 2: r=0.095; P=.82; equation 3: r=0.119; P=.78); however, standard 6MWT scores were significantly correlated with VT values (r=0.810; P=.02). The calculated submaximal treadmill scores and assessor 6MWT scores using technology also demonstrated a significant correlation (r=0.661; P=.04). CONCLUSIONS: This study demonstrated significant usability concerns regarding the accuracy of a self-administered 6MWT using the EasyMeasure app. However, the strong and significant correlation between the 6MWT and VT values demonstrates the potential of the 6MWT to measure functional capacity for community-based exercise screening and patient monitoring.

The Exercise Oncology Knowledge Mobilization Initiative: An International Modified Delphi Study.

INTRODUCTION: Exercise is vital to health and well-being after a cancer diagnosis yet is poorly integrated in cancer care. Knowledge mobilization (KM) is essential to enhance exercise opportunities. We aimed to (1) develop and refine a list of highly important exercise oncology research and KM themes and (2) establish the relative importance of the themes for supporting the implementation of exercise as a standard of care for people living with and beyond cancer. METHODS: Informed by the Co-Produced Pathway to Impact KM framework, a modified Delphi study approach was used to develop, rate, and rank exercise oncology research and KM themes through an international stakeholder workshop and a three-round iterative online survey. Open-ended stakeholder feedback from cancer survivors, healthcare practitioners (HCPs), qualified exercise professionals (QEPs), policy makers, and researchers was used to update themes between survey rounds. Themes were ranked from highest to lowest importance and agreement was examined across all stakeholders and within stakeholder groups. RESULTS: A total of 269 exercise oncology stakeholders from 13 countries participated in the study. Twelve final exercise oncology research and KM themes were produced. The final top ranked research themes were related to: (1) QEP integration into primary cancer care teams, (2) Exercise oncology education for HCPs, and (3) Accessibility of cancer exercise programs & support services. There was statistically significant agreement between stakeholders (p<0.001) and within stakeholder groups (p's≤0.02) on the general rankings of themes (i.e., some themes generally ranked higher and lower compared to others). Low Kendall's W statistics indicated variability related to the specific ranked order of the themes between stakeholders and within stakeholder groups. Moreover, there were key differences in the rankings for specific themes between policy makers and other stakeholder groups that highlight potentially important discordance in the research and KM priorities for policy makers that warrants further study. CONCLUSION: These findings can be used to guide initiatives and align stakeholders on priorities to support exercise implementation as a standard of cancer care. Additional research is needed to better understand the differences in the proposed research and KM priorities across stakeholders.

Comparing the reporting and conduct quality of exercise and pharmacological randomised controlled trials: a systematic review.

OBJECTIVE: Evaluate the quality of exercise randomised controlled trial (RCT) reporting and conduct in clinical populations (ie, adults with or at risk of chronic conditions) and compare with matched pharmacological RCTs. DESIGN: Systematic review. DATA SOURCES: Embase (Elsevier), PubMed (NLM) and CINAHL (EBSCO). STUDY SELECTION: RCTs of exercise in clinical populations with matching pharmacological RCTs published in leading clinical, medical and specialist journals with impact factors ≥15. REVIEW METHODS: Overall RCT quality was evaluated by two independent reviewers using three research reporting guidelines (ie, Consolidated Standards of Reporting Trials (CONSORT; pharmacological RCTs)/CONSORT for non-pharmacological treatments; exercise RCTs), CONSORT-Harms, Template for Intervention Description and Replication) and two risk of bias assessment (research conduct) tools (ie, Cochrane Risk of Bias, Jadad Scale). We compared research reporting and conduct quality within exercise RCTs with matched pharmacological RCTs, and examined factors associated with quality in exercise and pharmacological RCTs, separately. FINDINGS: Forty-eight exercise RCTs (11 658 patients; median sample n=138) and 48 matched pharmacological RCTs were evaluated (18 501 patients; median sample n=160). RCTs were conducted primarily in cardiovascular medicine (43%) or oncology (31%). Overall quality score (composite of all research reporting and conduct quality scores; primary endpoint) for exercise RCTs was 58% (median score 46 of 80; IQR: 39-51) compared with 77% (53 of 68; IQR: 47-58) in the matched pharmacological RCTs (p≤0.001). Individual quality scores for trial reporting and conduct were lower in exercise RCTs compared with matched pharmacological RCTs (p≤0.03). Factors associated with higher overall quality scores for exercise RCTs were journal impact factor (≥25), sample size (≥152) and publication year (≥2013). CONCLUSIONS AND RELEVANCE: Research reporting and conduct quality within exercise RCTs is inferior to matched pharmacological RCTs. Suboptimal RCT reporting and conduct impact the fidelity, interpretation, and reproducibility of exercise trials and, ultimately, implementation of exercise in clinical populations. PROSPERO REGISTRATION NUMBER: CRD42018095033.

Characterizing the Exercise Behaviour, Preferences, Barriers, and Facilitators of Cancer Survivors in a Rural Canadian Community: A Cross-Sectional Survey.

Barriers, facilitators, and motivators to exercise for cancer survivors living in urban settings are well described in the literature. However, there is a lack of comparable information for cancer survivors living in rural communities. We describe the exercise behaviours, barriers, facilitators, and motivators to exercise participation of cancer survivors living in a rural Canadian community. Adult cancer survivors with a primary address in a rural region of Ontario, Canada, who had visited a community hospital in the previous five years were mailed a cross-sectional survey assessing current exercise volume (minutes of moderate-to-vigorous aerobic and resistance exercise), as well as exercise preferences, barriers, and facilitators. Seventy-two survivors (mean age 65 years) completed the survey (16% response rate). A majority of respondents were diagnosed with breast cancer (49%) in the last 5 years (61%). Aerobic- and resistance-training guidelines for cancer survivors were met by 38% and 10% of respondents, respectively. Physical side effects were the most common barrier to exercise during treatment (65%) and post-treatment (35%). Being unaware of available exercise programs, time for exercise, distance to exercise services, and cost were commonly reported barriers during and post-treatment (reported by 10-22%). Respondents reported needing information from a qualified exercise professional (46%), access to a gym (33%) and exercise equipment (26%), and social support (25%) to facilitate exercise participation. Consistent with urban-based cancer survivors, most rural survivors surveyed in this study were not meeting the physical-activity guidelines and reported numerous exercise barriers. These findings can serve as a resource for this and similar rural communities when developing community-based exercise-support services for cancer survivors.

Young Adult Cancer Survivorship: Recommendations for Patient Follow-up, Exercise Therapy, and Research.

Survivors of adolescent and young adult cancers (AYAs) often live 50 to 60 years beyond their diagnosis. This rapidly growing cohort is at increased risk for cancer- and treatment-related 'late effects' that persist for decades into survivorship. Recognition of similar issues in pediatric cancer survivors has prompted the development of evidence-based guidelines for late effects screening and care. However, corresponding evidence-based guidelines for AYAs have not been developed. We hosted an AYA survivorship symposium for a large group of multidisciplinary AYA stakeholders (approximately 200 were in attendance) at Princess Margaret Cancer Centre (Toronto, Ontario, Canada) to begin addressing this disparity. The following overview briefly summarizes and discusses the symposium's stakeholder-identified high-priority targets for late effects screening and care and highlights knowledge gaps to direct future research in the field of AYA survivorship. This overview, although not exhaustive, is intended to stimulate clinicians to consider these high-priority screening and care targets when seeing survivors in clinical settings and, ultimately, to support the development of evidence-based late effects screening and care guidelines for AYAs.

Preferences for exercise and physical activity support in adolescent and young adult cancer survivors: a cross-sectional survey.

PURPOSE: Exercise and physical activity (hereafter, collectively referred to as PA) preferences and benefits are becoming increasingly well characterised in cancer survivors, yet evidence from adolescent and young adult cancer survivors (AYAs) is scant. We describe the overall PA behaviour and support preferences of AYAs and explore subgroup differences to inform AYA-specific research and support. METHODS: AYAs diagnosed with cancer between the ages of 18-39 years, irrespective of current age, were approached in clinic at a large cancer centre for this cross-sectional survey that assessed self-reported demographics, medical history, PA behaviour and PA support preferences. RESULTS: A total of 318 AYAs completed the survey. Approximately 40% of AYAs were not meeting PA guidelines, and only 5% reported engagement with cancer PA support services. Most AYAs wanted PA support (78%), to increase PA levels (70%), and were interested in engaging in PA interventions that were individually supervised (82%), home-based (79%), performed ≥ 3 days/week (75%) and for ≥ 30 minutes/session (78%), offered following treatment (63%), restricted by age (63%), and involved strength (83%), walking (78%), and flexibility (75%) exercise. PA preferences most often differed according to sex, treatment status, current PA behaviour and PA support setting. CONCLUSION: AYAs have a great capacity and interest in specific types of PA support. Poor engagement with existing PA support services highlights the need for further AYA-specific research. Better understanding of AYAs' unique PA behaviour and support preferences can inform the development of urgently needed research and support services for this understudied and rapidly growing population.

Body image concerns of young adult cancer survivors: A brief report.

BACKGROUND: The purpose of this study was to describe body image among young adult (YA) cancer survivors and examine relationships between body image and personal, medical, and psychosocial variables. Methods: YAs (n = 522; Mage = 34 ± 6 years) completed an online survey and data were analyzed using descriptive statistics, bivariate correlations, and appropriate tests of mean differences. Results: Higher body image concerns were related to less time since diagnosis, lower post-traumatic growth and social support, greater distress, and a higher number of treatments received (rs = .09 to .42; ps < .05). Body image concerns were higher for those currently on treatment (p < .05). Conclusions: Findings suggest greater attention to YAs' body image is necessary. Specifically, longitudinal research and the development of strategies dedicated to reducing body image concerns among YAs are needed.

Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy.

BACKGROUND: Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)-related and all-cause mortality. However, routine measurement of CRF is not always feasible. OBJECTIVES: The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO2peak) (measure of CRF) early post-breast cancer therapy to help inform CVD risk. METHODS: Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 ± 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO2peak using a cycle ergometer. Regression models were used to examine the association between VO2peak and clinical, imaging, and cardiac biomarkers individually and in combination. RESULTS: Among 147 patients (age 52.2 ± 9.3 years), the mean VO2peak was 19.1 ± 5.0 mL O2·kg-1·min-1 (84.2% ± 18.7% of predicted); 44% had a VO2peak below threshold for functional independence (<18 mL O2·kg-1·min-1). In multivariable analysis, absolute global longitudinal strain (GLS) (ß = 0.58; P = 0.007), age per 10 years (ß: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (ß = -0.45; P = 0.038) were associated with VO2peak. GLS added incremental value in explaining the variability in VO2peak. The combination of age ≥50 years, E/e' ≥7.8, and GLS <18% identified a high probability (85.7%) of compromised functional independence, whereas age <50 years, E/e' <7.8, and GLS ≥18% identified a low probability (0%). High-sensitivity troponin I and B-type natriuretic peptide were not associated with VO2peak. CONCLUSIONS: Readily available clinical measures were associated with VO2peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk.

The impact of exercise on growth factors (VEGF and FGF2): results from a 12-month randomized intervention trial.

BACKGROUND: Vascular endothelial growth factor (VEGF) and Fibroblast growth factor-2 (FGF2) are angiogenic cytokines in normal tissues and tumors. Evidence suggests that increased growth factor expression in adipose tissue leads to improved vascularity and decreased hypoxia, fibrosis, and inflammation, which may, in turn, reduce post-menopausal breast cancer risk. OBJECTIVE: We investigated whether or not exercise had dose-response effects on levels of plasma VEGF and FGF2 in postmenopausal women. METHODS: Four hundred previously inactive but healthy postmenopausal women aged 50-74 years of age were randomized to 150 or 300 min per week of aerobic exercise in a year-long exercise intervention. VEGF and FGF2 were measured from fasting serum samples with a custom-plex multiplex assay. RESULTS: A high compared to moderate volume of aerobic exercise did not cause chronic changes in plasma VEGF or FGF2 levels in intention-to-treat or per-protocol analyses. CONCLUSIONS: We did not detect differences in growth factor levels related to increasing doses of exercise. It is unlikely that changes in VEGF and FGF2 levels mediate the reduction in risk of post-menopausal breast cancer development in associated with increased levels of exercise. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01435005.

Efficacy of Exercise Therapy on Cardiorespiratory Fitness in Patients With Cancer: A Systematic Review and Meta-Analysis.

Purpose To evaluate the effects of exercise therapy on cardiorespiratory fitness (CRF) in randomized controlled trials (RCTs) among patients with adult-onset cancer. Secondary objectives were to evaluate treatment effect modifiers, safety, and fidelity. Methods A systematic search of PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library was conducted to identify RCTs that compared exercise therapy to a nonexercise control group. The primary end point was change in CRF as evaluated by peak oxygen consumption (VO2peak; in mL O2 × kg-1 × min-1) from baseline to postintervention. Subgroup analyses evaluated whether treatment effects differed as a function of exercise prescription (ie, modality, schedule, length, supervision), study characteristics (ie, intervention timing, primary cancer site), and publication year. Safety was defined as report of any adverse event (AE); fidelity was evaluated by rates of attendance, adherence, and loss to follow-up. Results Forty-eight unique RCTs that represented 3,632 patients (mean standard deviation age, 55 ± 7.5 years; 68% women); 1,990 (55%) and 1,642 (45%) allocated to exercise therapy and control/usual care groups, respectively, were evaluated. Exercise therapy was associated with a significant increase in CRF (+2.80 mL O2 × kg-1 × min-1) compared with no change (+0.02 mL O2 × kg-1 × min-1) in the control group (weighted mean differences, +2.13 mL O2 × kg-1 × min-1; 95% CI, 1.58 to 2.67; I2, 20.6; P < .001). No statistical significant differences were observed on the basis of any treatment effect modifiers. Thirty trials (63%) monitored AEs; a total of 44 AEs were reported. The mean standard deviation loss to follow-up, attendance, and adherence rates were 11% ± 13%, 84% ± 12%, and 88% ± 32%, respectively. Conclusion Exercise therapy is an effective adjunctive therapy to improve CRF in patients with cancer. Our findings support the recommendation of exercise therapy for patients with adult-onset cancer.

Association of Exercise With Mortality in Adult Survivors of Childhood Cancer.

Importance: Adult survivors of childhood cancer are at excess risk for mortality compared with the general population. Whether exercise attenuates this risk is not known. Objective: To examine the association between vigorous exercise and change in exercise with mortality in adult survivors of childhood cancer. Design, Setting, and Participants: Multicenter cohort analysis among 15 450 adult cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970 and 1999 enrolled in the Childhood Cancer Survivor Study, with follow-up through December 31, 2013. Exposures: Self-reported vigorous exercise in metabolic equivalent task (MET) hours per week. The association between vigorous exercise and change in vigorous exercise and cause-specific mortality was assessed using multivariable piecewise exponential regression analysis to estimate rate ratios. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary end points were cause-specific mortality (recurrence/progression of primary malignant neoplasm and health-related mortality). Outcomes were assessed via the National Death Index. Results: The 15 450 survivors had a median age at interview of 25.9 years (interquartile range [IQR], 9.5 years) and were 52.8% male. During a median follow-up of 9.6 years (IQR, 15.5 years), 1063 deaths (811 health-related, 120 recurrence/progression of primary cancer, 132 external/unknown causes) were documented. At 15 years, the cumulative incidence of all-cause mortality was 11.7% (95% CI, 10.6%-12.8%) for those who exercised 0 MET-h/wk, 8.6% (95% CI, 7.4%-9.7%) for 3 to 6 MET-h/wk, 7.4% (95% CI, 6.2%-8.6%) for 9 to 12 MET-h/wk, and 8.0% (95% CI, 6.5%-9.5%) for 15 to 21 MET-h/wk (P < .001). There was a significant inverse association across quartiles of exercise and all-cause mortality after adjusting for chronic health conditions and treatment exposures (P = .02 for trend). Among a subset of 5689 survivors, increased exercise (mean [SD], 7.9 [4.4] MET-h/wk) over an 8-year period was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise (rate ratio, 0.60; 95% CI, 0.44-0.82; P = .001). Conclusions and Relevance: Vigorous exercise in early adulthood and increased exercise over 8 years was associated with lower risk of mortality in adult survivors of childhood cancer.

Effects of high-intensity interval training on fatigue and quality of life in testicular cancer survivors.

BACKGROUND: Testicular cancer survivors (TCS) are at increased risk of cancer-related fatigue (CRF), psychosocial impairment, and poor mental health-related quality of life (HRQoL). Here, we examine the effects of high-intensity interval training (HIIT) on patient-reported outcomes (PROs) in TCS. Secondarily, we explore cardiorespiratory fitness as a mediator of intervention effects and select baseline characteristics as moderators of intervention effects. METHODS: TCS (n = 63) were randomly assigned to 12 weeks of supervised HIIT or usual care (UC). PROs included CRF, depression, anxiety, stress, self-esteem, sleep quality, and HRQoL assessed at baseline, post-intervention, and 3-month follow-up. RESULTS: TCS (median 7 years postdiagnosis) completed 99% of training sessions and achieved 98% of target training intensity. ANCOVA revealed that, compared to UC, HIIT significantly improved post-intervention CRF (p = 0.003), self-esteem (p = 0.029), and multiple HRQoL domains (ps ≤ 0.05). Effects on CRF (p = 0.031) and vitality (p = 0.015) persisted at 3-month follow-up. Cardiorespiratory fitness changes mediated CRF and HRQoL improvements. CRF effects were larger for TCS with an inactive lifestyle, lower fitness, higher testosterone, and clinical fatigue at baseline. CONCLUSIONS: HIIT significantly improves CRF and HRQoL in TCS. Mediation by cardiorespiratory fitness and moderation by clinical characteristics suggests opportunities for targeted exercise interventions to optimise PROs in TCS.

Effects of high-intensity aerobic interval training on cardiovascular disease risk in testicular cancer survivors: A phase 2 randomized controlled trial.

BACKGROUND: Testicular cancer survivors (TCS) have an increased risk of treatment-related cardiovascular disease (CVD), which may limit their overall survival. We evaluated the effects of high-intensity aerobic interval training (HIIT) on traditional and novel CVD risk factors and surrogate markers of mortality in a population-based sample of TCS. METHODS: This phase 2 trial (ClinicalTrials.gov identifier NCT02459132) randomly assigned 63 TCS to usual care (UC) or 12 weeks of supervised HIIT (ie, alternating periods of vigorous-intensity and light-intensity aerobic exercise). The primary outcome was peak aerobic fitness (VO2peak ) assessed via a treadmill-based maximal cardiorespiratory exercise test. Secondary endpoints included CVD risk (eg, Framingham Risk Score), arterial health, parasympathetic nervous system function, and blood-based biomarkers. RESULTS: Postintervention VO2peak data were obtained for 61 participants (97%). HIIT participants attended 99% of the exercise sessions and achieved 98% of the target exercise intensity. Analysis of covariance demonstrated that HIIT was superior to UC for improving VO2peak (adjusted between-group mean difference, 3.7 mL O2 /kg/min; 95% confidence interval, 2.4-5.1 [P<.001]) and multiple secondary outcomes including CVD risk (P = .011), arterial thickness (P<.001), arterial stiffness (P<.001), postexercise parasympathetic reactivation (P = .001), inflammation (P = .045), and low-density lipoprotein (P = .014). Overall, HIIT reduced the prevalence of modifiable CVD risk factors by 20% compared with UC. CONCLUSIONS: This randomized trial provides the first evidence that HIIT improves cardiorespiratory fitness, multiple pathways of CVD risk, and surrogate markers of mortality in TCS. These findings have important implications for the management of TCS. Further research concerning the long-term effects of HIIT on CVD morbidity and mortality in TCS is warranted. Cancer 2017;123:4057-65. © 2017 American Cancer Society.