Translating energy balance research from the bench to the clinic to the community: Parallel animal-human studies in cancer.

Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer toward practice changes. This review summarizes key topics discussed to advance research on the role of energy balance, including physical activity, body composition, and dietary intake, on cancer development, cancer outcomes, and healthy survivorship.

Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer.

Multiple organizations around the world have issued evidence-based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health-related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home-based or community-based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Weight management and physical activity throughout the cancer care continuum.

Mounting evidence suggests that weight management and physical activity (PA) improve overall health and well being, and reduce the risk of morbidity and mortality among cancer survivors. Although many opportunities exist to include weight management and PA in routine cancer care, several barriers remain. This review summarizes key topics addressed in a recent National Academies of Science, Engineering, and Medicine workshop entitled, "Incorporating Weight Management and Physical Activity Throughout the Cancer Care Continuum." Discussions related to body weight and PA among cancer survivors included: 1) current knowledge and gaps related to health outcomes; 2) effective intervention approaches; 3) addressing the needs of diverse populations of cancer survivors; 4) opportunities and challenges of workforce, care coordination, and technologies for program implementation; 5) models of care; and 6) program coverage. While more discoveries are still needed for the provision of optimal weight-management and PA programs for cancer survivors, obesity and inactivity currently jeopardize their overall health and quality of life. Actionable future directions are presented for research; practice and policy changes required to assure the availability of effective, affordable, and feasible weight management; and PA services for all cancer survivors as a part of their routine cancer care. CA Cancer J Clin 2018;68:64-89. © 2017 American Cancer Society.

Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial.

BACKGROUND: Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. METHODS: Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. RESULTS: Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). CONCLUSIONS: Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.

Exercise oncology clinical trials during treatments: a commentary to address the safety concerns of human subjects regulatory reviewers and committees.

Exercise oncology clinical trials contribute to the advancement of our scientific knowledge and to the safety and care of patients diagnosed with cancer. Nevertheless, regulatory reviewers and committees may not be familiar with the well-documented long-term health benefits and safety of the regular practice of physical activity. Moreover, they may not see how the benefits outweigh the risks in the context where patients diagnosed with cancer are typically seen as vulnerable. Therefore, we would like to provide a purpose-built overview of exercise oncology clinical trials for members involved in institutional review committees, including the Scientific Review Committee (SRC), the Institutional Review Board (IRB), and the Data Safety Monitoring Committee (DSMC) to facilitate a greater understanding of the safety and benefits of physical activity during cancer treatments. Communication is key to improve the success of exercise oncology clinical trials, which are vital for patients diagnosed with cancer.

An initiative to implement a triage and referral system to make exercise and rehabilitation referrals standard of care in oncology.

BACKGROUND: Clinical guidelines suggest that patients should be referred to exercise while undergoing cancer treatment. Oncology clinicians report being supportive of exercise referrals but not having the time to make referrals. Toward the goal of making exercise referrals standard of care, we implemented and evaluated a novel clinical workflow. METHODS: For this QI project, a rehabilitation navigator was inserted in chemotherapy infusion clinics. Patients were offered a validated electronic triage survey. Exercise or rehabilitation recommendations were communicated to patients during a brief counseling visit by the rehabilitation navigator. The implementation approach was guided by the EPIS framework. Acceptability and feasibility were assessed. RESULTS: Initial meetings with nursing and cancer center leadership ensured buy-in (exploration). The education of medical assistants contributed to the adoption of the triage process (preparation). Audit and feedback ensured leadership was aware of medical assistants' performance (implementation). 100% of medical assistants participated in implementing the triage tool. A total of 587 patients visited the infusion clinics during the 6-month period when this QI project was conducted. Of these, 501 (85.3%) were offered the triage survey and 391 (78%) completed the survey (acceptability). A total of 176 (45%) of triaged patients accepted a referral to exercise or rehabilitation interventions (feasibility). CONCLUSIONS: Implementation of a validated triage tool by medical assistants and brief counseling by a rehabilitation navigator resulted in 45% of infusion patients accepting a referral to exercise or rehabilitation. The triage process showed promise for making exercise referrals standard of care for patients undergoing cancer treatment.

Evaluating the relationship between physical activity and quality of life in a racially diverse sample of breast cancer survivors.

PURPOSE: Physical activity (PA) has been shown to improve quality of life (QoL) in predominantly White cancer survivors. Very few studies have examined the association between PA and QoL among Black breast cancer survivors (BCS). We investigated the association between PA and multiple QoL domains and the effects of race on the proposed association in a racially diverse group of BCS. METHODS: This was an exploratory study using secondary data from a completed 12-month randomized controlled  trial (RCT). Mixed effects models were tested on a subset of participants in the control and exercise groups of the RCT. The primary outcomes were changes in the QoL domains (baseline to 12 months post baseline). RESULTS: There were 173 participants included in this analysis, averaging 59 years of age; about 33% of the participants were Black women. There were no significant differences in the QoL outcomes between the control and exercise groups at 12 months post baseline. Race was not a significant moderator. Exercise improved emotional/mental wellbeing and body image as it relates to social barriers at 12 months post baseline in Black and White BCS, but the changes in these outcomes were only statistically significant in White BCS (p < 0.05). CONCLUSIONS: Results show that exercise can improve multiple QoL domains over time in Black BCS. However, the significance of the effect on QoL was isolated to White BCS. The small sample size in Black women could constrain the statistical significance of observed effects. Future studies are warranted to assess associations between exercise and QoL in larger samples of Black women.

Online-delivered resistance exercise intervention among racially diverse breast cancer survivors: Feasibility, acceptability, and exploratory outcomes of B-REP.

PURPOSE: The aims are to determine the feasibility of an online-delivered resistance exercise program among racially diverse breast cancer survivors and to conduct an exploratory analysis of the intervention on muscular strength, physical activity levels, health-related quality of life, and self-efficacy. METHODS: A 2-arm randomized controlled trial study design with assessments at pre- and post-intervention was used. Participants (n = 52) were recruited from clinics at the host institution and randomized to either intervention (n = 28) or minimal contact control (MCC) conditions (n = 24). All participants received a 12-week individualized resistance exercise prescription based on their baseline functional strength assessment. Intervention participants exercised one-on-one once per week over Zoom with an exercise trainer. MCC participants received no supervision. Descriptive statistics were used to determine feasibility and acceptability (primary outcomes). Repeated measures ANOVAs were used to examine exploratory outcomes. RESULTS: The intervention demonstrated high rates for feasibility outcomes of enrollment (80.0%) and post-intervention assessment completion (92.9%). Acceptability outcomes were high for session attendance (98.0%) and satisfaction (Mscore = 4.87 out of 5, SD = .18). The intervention group increased upper- (p < .01) and lower- (p < .02) body strength compared to MCC condition. CONCLUSIONS: The intervention was feasible, acceptable, and demonstrated increases in muscular strength. Limitations include a small sample recruited from one cancer center. Future research is needed to determine longitudinal impacts of resistance exercise on survivorship outcomes. Online-delivered resistance exercise shows promising efficacy among racially diverse breast cancer survivors. CLINICALTRIALS: gov registration: NCT04562233 on September 18, 2020.

Implementing a behavioral physical activity program in children and adolescent survivors of childhood cancer: a pilot randomized controlled trial.

Purpose We aimed to document the acceptability (enrollment rate) and feasibility (phone call delivery rate) of implementing a behavioral PA intervention over 12 weeks, in addition to documenting its effects on patient-reported outcomes and physical functioning. This study also describes the costs of carrying out a behavioral PA intervention. A total of 40 participants were randomized in a 1:1 ratio. The tailored behavioral PA intervention was developed based on the most recent PA guidelines in pediatric oncology and on the COM-B framework to enact PA behavior changes. The prescription (frequency, intensity, time and type (FITT)) was adjusted each week during the weekly support calls. The control group did not receive the intervention. 26 males and 14 females (13.6 years old on average and 2.9 years post-cancer treatment on average) participated in our study. The acceptability rate was 90.9% and the feasibility rate was > 85%. We found that 85% improved PA frequency, 80% improved PA intensity, 100% improved PA time, and 50.0% achieved the recommended PA guidelines. No adverse events were reported over the duration of the intervention. Physical function improved with longer 6-minute walk distances in the intervention group (465.8 ± 74.5 m) than in the control group (398.7 ± 92.9 m) (p = 0.016). PROs scores for all participants were within the limits of the normal range. The estimated cost per participant of carrying out this intervention was USD $126.57. Our 12-week behavioral PA intervention, based on the COM-B framework, was found to be acceptable, feasible and safe in childhood cancer survivors. This study is an important step in the right direction to make exercise standard practice in pediatric oncology.

Exploring Quality of Life Experiences and Concerns of Black Breast Cancer Survivors: a Narrative Approach.

Black breast cancer survivors (BCS) in comparison with White BCS are more likely to experience suboptimal quality of life (QoL). QoL is a multi-dimensional concept that focuses on different aspects of well-being (e.g., emotional well-being). There is limited evidence on the perspectives and experiences of QoL (e.g., the influence of breast cancer on QoL) and the QoL concerns (e.g., negative perceptions of body appearance) among Black BCS. The purpose of this study was to explore the QoL experiences and QoL concerns of Black BCS. Primary data was collected in semi-structured interviews and analyzed using a thematic analysis. A narrative approach (detailed stories or life experiences of a small group of people) was used to better understand the research topic among the target group. Ferrell's Conceptual Framework on QoL in Breast Cancer was used to guide the development of the interview questions, codes, and themes. There were 10 Black BCS, averaging 58 years of age. Two coders achieved a moderate level of agreement (i.e., Kappa) of 0.77. Five major themes were identified: defining QoL (what QoL means to them), behavioral changes (e.g., altering behaviors due to cancer), phases of cancer (e.g., breast cancer diagnosis), QoL experiences and factors affecting QoL, and impactful statements from cancer survivors (other meaningful information shared by the participants). The survivors reported multiple QoL concerns and body image issues. The study findings warrant cancer education interventions or programs to address the relevant survivorship issues of Black BCS.

Academic verb knowledge of DHH college students and their hearing peers.

This study addressed the critical gap in research on the academic English vocabulary knowledge of deaf and hard-of-hearing (DHH) students at the college level, with a specific focus on academic English verbs. An English vocabulary test was developed to assess knowledge of academic verbs at three distinct corpus-defined lexical frequency ranges. The test was administered to the DHH students along with two comparison groups of college peers-students of English as an Additional Language (EAL)1 and hearing native-English-speaking students. Results revealed near-ceiling performance by hearing native speakers but significant vocabulary challenges in the DHH and EAL learner groups, who exhibited parallel lexical knowledge. Learner group performance increased as verb frequency range increased and as overall English proficiency level increased. The findings demonstrate that lexical frequency effects guide English verb acquisition in the targeted populations.2.

Exercise Training Is Associated With Treatment Response in Liver Fat Content by Magnetic Resonance Imaging Independent of Clinically Significant Body Weight Loss in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Exercise training is crucial in the management of nonalcoholic fatty liver disease (NAFLD); however, whether it can achieve clinically meaningful improvement in liver fat is unclear. We investigated the association between exercise training and the achievement of validated thresholds of MRI-measured treatment response. METHODS: Randomized controlled trials in adults with NAFLD were identified through March 2022. Exercise training was compared with no exercise training. The primary outcome was ≥30% relative reduction in MRI-measured liver fat (threshold required for histologic improvement in nonalcoholic steatohepatitis activity, nonalcoholic steatohepatitis resolution, and liver fibrosis stage). Different exercise doses were compared. RESULTS: Fourteen studies (551 subjects) met inclusion criteria (mean age 53.3 yrs; body mass index 31.1 kg/m 2 ). Exercise training subjects were more likely to achieve ≥30% relative reduction in MRI-measured liver fat (odds ratio 3.51, 95% confidence interval 1.49-8.23, P = 0.004) than those in the control condition. An exercise dose of ≥750 metabolic equivalents of task min/wk (e.g., 150 min/wk of brisk walking) resulted in significant treatment response (MRI response odds ratio 3.73, 95% confidence interval 1.34-10.41, P = 0.010), but lesser doses of exercise did not. Treatment response was independent of clinically significant body weight loss (>5%). DISCUSSION: Independent of weight loss, exercise training is 3 and a half times more likely to achieve clinically meaningful treatment response in MRI-measured liver fat compared with standard clinical care. An exercise dose of at least 750 metabolic equivalents of task-min/wk seems required to achieve treatment response. These results further support the weight-neutral benefit of exercise in all patients with NAFLD.

The effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors.

PURPOSE: Cancer and its treatments accelerate biological aging. This analysis tested the hypothesis that exercise and diet reduce oxidative stress and prevent telomere shortening in breast cancer survivors. METHODS: In a 2 × 2 factorial design, 342 breast cancer survivors who were insufficiently physically active and had overweight or obesity at enrollment were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. The endpoints of this analysis were the change from baseline to week 52 in 8-iso-prostaglandin F2α (8-iso-PGF2α) and lymphocyte telomere length. RESULTS: Baseline telomere length was shorter than age-adjusted normative values (median difference: - 1.8 kilobases; 95% CI - 2.4, - 1.1); equivalent to 21 years (95% CI 17, 25) of accelerated chronological aging. Compared to control, exercise alone did not change 8-iso-PGF2α [9.9%; 95% confidence interval (CI) - 1.0, 20.8] or telomere length (13.8%; 95% CI - 15.6, 43.3). Compared to control, diet alone was associated with reduced 8-iso-PGF2α (- 10.5%; 95% CI - 19.5, - 1.5) but did not change telomere length (12.1%; 95% CI - 17.2, 41.3). Compared to control, exercise plus diet was associated with reduced 8-iso-PGF2α (- 9.8%; 95% CI - 18.7, - 0.9) but did not change telomere length (- 8.5%; 95% CI - 32.1, 15.2). Change in 8-iso-PGF2α did not correlate with change in telomere length (r = 0.07; 95% CI - 0.07, 0.20). CONCLUSION: In breast cancer survivors, diet alone or exercise plus diet were associated with reduced oxidative stress but did not change telomere length. This analysis may inform future trials that aim to optimize healthy aging in cancer survivors.

Women with metastatic breast cancer don't just follow step-count trends, they exceed them: an exploratory study.

PURPOSE: Metastatic breast cancer (MBC) patients are living longer at the cost of several side effects, affecting their physical and mental health. Physical activity can help women with MBC to improve their wellbeing. Technology-based exercise interventions have shown promising outcomes; however, studies that document their benefits on health behaviors are lacking. Therefore, we aimed to document the impact of virtual assistant technology on enhancing daily step counts in women with MBC. METHODS: A total of 38 women with MBC participated in the 90-day Nurse AMIE (Addressing Metastatic Individuals Everyday) for Amazon Echo Show study, an artificial intelligence-based supportive care intervention. Each day, Nurse AMIE asked four symptom questions (sleep, pain, fatigue, and distress) and daily step counts. Based on participants' answers, an algorithm provided an activity to assist with symptom management. RESULTS: During the first week of the intervention, mean step counts per day were 4935 ± 2884, and during the last week of the intervention, mean step counts per day were 1044 steps higher, for an average of 5979 ± 2651 steps. Non-significant differences were observed between the first and last week (p = 0.211) and between the first and last day (p = 0.099), despite an improvement of 21.2% over time and significant differences between baseline and the other days. CONCLUSION: Women with MBC benefited from the Nurse AMIE for Amazon Echo Show intervention. Despite improvements over time (> 20%), we cannot conclude that the intervention significantly enhanced participants' daily step counts. Larger studies using virtual assistant technologies are required, and this study should be considered a first step in this direction.

NASHFit: A randomized controlled trial of an exercise training program to reduce clotting risk in patients with NASH.

BACKGROUND AND AIMS: NASH is a common disease associated with increased rates of thromboembolism (TE). Although exercise training can lessen thrombotic risk in patients with vascular disease, whether similar findings are observed in patients with NASH is open for study. APPROACH AND RESULTS: We conducted a 20-week randomized controlled clinical trial involving patients with biopsy-confirmed NASH. Patients were randomly assigned (2:1 ratio) to receive either an exercise training program or standard clinical care. The primary endpoint was change in plasminogen activator inhibitor 1 (PAI-1) level, an established thrombotic biomarker. Twenty-eight patients were randomly assigned (18 exercise training and 10 standard clinical care). PAI-1 level was significantly decreased by exercise training when compared to standard clinical care (-40 ± 100 vs. +70 ± 63 ng/ml; p = 0.02). Exercise training decreased MRI proton density fat fraction (MRI-PDFF; -4.7 ± 5.6 vs. 1.2 ± 2.8% absolute liver fat; p = 0.01); 40% of exercise subjects had a ≥30% relative reduction in MRI-PDFF (histological response threshold) compared to 13% for standard of care (p < 0.01). Exercise training improved fitness (VO2 peak, +3.0 ± 5.6 vs. -1.8 ± 5.1 ml/kg/min; p = 0.05) in comparison to standard clinical care. CONCLUSIONS: This clinical trial showed that, independent of weight loss or dietary change, exercise training resulted in a significantly greater decrease in thrombotic risk than standard clinical care in patients with NASH, in parallel with MRI-PDFF reduction and improvement in fitness. Future studies are required to determine whether exercise training can directly impact patient outcomes and lower rates of TE.

Chronic pain in children and adolescents diagnosed with cancer: the challenge of mitigating the pain and the potential of integrating exercise into pain management.

BACKGROUND: Pain is one of the most common and distressing symptoms experienced by children and adolescents diagnosed with cancer. It is vital that children and adolescents receive adequate pain management early on in their cancer treatments to mitigate pain and cancer-related symptoms. Exercise training shows particular promise in the management of acute and chronic pain among children and adolescents diagnosed with cancer. METHODS: This position paper comes to outline the challenge of mitigating pain in children and adolescents diagnosed with cancer, and the potential benefits of integrating exercise training to the management of chronic pain in this population in need. RESULTS: Integrating exercise training into the care and pain management of children and adolescents diagnosed with cancer who have chronic pain would have the advantage of addressing several shortcomings of pain medication. Pain medication aims to temporarily manage or reduce pain; it does not have the potential to directly improve a patient's physical condition in the way that exercise training can. The current paucity of data available on the use of exercise training as a complementary treatment to pain medications to reduce chronic pain in children and adolescents diagnosed with cancer allows only for hypotheses on the effectiveness of this pain management modality. CONCLUSION: More research on this important topic is necessary and mitigating pain effectively while also reducing the use of opioid pain medication is an important goal shared by patients, their families, clinicians, and researchers alike. Future research in this area has great potential to inform clinical care, clinical care guidelines, and policy-making decisions for pain management in children and adolescents diagnosed with cancer who experience chronic pain.

Technology-based supportive care for metastatic breast cancer patients.

PURPOSE: Metastatic breast cancer (MBC) patients are living longer. However, symptom burden remains a significant issue. Technology-based interventions may assist. The purpose of this study was to test a virtual assistant for addressing symptoms in MBC using the Amazon Echo Show with Alexa. METHODS: In this partial crossover randomized trial, the immediate treatment group was exposed to the intervention, called Nurse AMIE (Addressing Metastatic Individuals Everyday) for 6 months. The comparison group was unexposed for the first 3 months and then exposed for 3 months. The randomized controlled trial (RCT) during the first 3 months allowed for the evaluation of intervention effects on symptoms and function. The partial crossover maximized exposure to the intervention for evaluation of feasibility, usability, and satisfaction. RCT outcome data were collected at baseline and 3 months. Feasibility, usability, and satisfaction data were collected throughout the first 3 months of intervention exposure. RESULTS: Forty-two MBC patients were randomized (1:1). Participants were 53 ± 11 years old and 4 ± 7 years from diagnosis with metastatic disease. No significant effects on psychosocial distress, pain, sleep disturbance, fatigue (vitality), quality of life, or chair stands were noted, despite high levels of acceptability (51%), feasibility (65%), and satisfaction (70%). CONCLUSION: A high level of participant acceptability, feasibility, usability, and satisfaction all suggest further research on this platform is warranted. The lack of statistically significant effects on symptoms, quality of life, and function may be the result of small sample size. GOV REGISTRATION NUMBER: NCT04673019 (registration date: December 17, 2020).

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.

Physical Activity and Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Physical activity offers promise to protect against multiple non-hepatic primary cancers. We performed a systematic review to quantify the association between physical activity and hepatocellular carcinoma (HCC) risk. METHODS: We searched the Cochrane Library, Embase, Medline and trial registries through December 2020 for studies that measured physical activity levels in adults at risk for HCC. The primary outcome was HCC. Subgroup analysis was performed limiting to vigorous physical activity. Proportions and random-effects odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. RESULTS: Seven studies met inclusion criteria, comprising 777,662 subjects (median age 55 years; 55% female). Greater amounts of physical activity were associated with less HCC (OR 0.65, 95% CI 0.45-0.95, p = 0.03) compared to lower amounts. Vigorous physical activity was associated with even less HCC (OR 0.62, 95% CI 0.49-0.79, p < 0.01). CONCLUSIONS: This meta-analysis demonstrates that greater amounts of physical activity are associated with lower odds of HCC. These results support the use of regular physical activity as an effective way to prevent HCC and provide helpful data to support a for future exercise-based interventional study to better define the optimal exercise prescription for patients at risk for primary liver cancer.

Patients with Nonalcoholic Steatohepatitis and Advanced Liver Disease Have the Lowest Cardiorespiratory Fitness.

BACKGROUND & AIMS: Cardiorespiratory fitness and liver fibrosis are independently associated with poor outcomes in patients with nonalcoholic steatohepatitis (NASH), however, conflicting reports exist about their relationship. We aimed to better characterize the relationship between cardiorespiratory fitness and liver histology in a cross-sectional study of patients with biopsy-proven NASH. METHODS: Participants aged 18-75 years completed VO2peak fitness assessment using symptom-limited graded exercise testing. Participants were compared by liver fibrosis stage and NAFLD Activity Score (NAS). Multivariable models were constructed to assess factors related to relative VO2peak, including liver fibrosis and NAS. RESULTS: Thirty-five participants with mean age 48 ± 12 years and body mass index 33.5 ± 7.6 kg/m2 were enrolled. Seventy-four percent of participants were female and 49% had diabetes. A dose-dependent relationship was found between relative VO2peak and liver fibrosis. Relative VO2peak was significantly lower in participants with advanced fibrosis (F3 disease- 15.7 ± 5.3 vs. ≤ F2 disease- 20.7 ± 5.9 mL/kg/min, p = 0.027). NAS > 5 was also associated with lower relative VO2peak (22.6 ± 5.7 vs. 16.5 ± 5.1 mL/kg/min, p = 0.012) compared to NAS ≤ 5. With multivariable modeling, advanced fibrosis remained independently predictive of relative VO2peak while NAS trended towards significance. DISCUSSION AND CONCLUSIONS: Advanced liver fibrosis is independently associated with cardiorespiratory fitness in patients with NASH. This may explain the incremental increase in mortality as liver fibrosis stage increases. Further research is needed to determine if exercise training can improve cardiorespiratory fitness across multiple stages of liver fibrosis and directly reduce morbidity and mortality in patients with NASH.