Radiation exposure during muscle development induces long-term decrements to skeletal muscle health, which contribute to reduced quality of life in childhood cancer survivors. Whether the effects of radiation on skeletal muscle are influenced by relevant physiological factors, such as obesity and exercise training remains unknown. Using skeletal muscle from our previously published work examining the effects of obesity and exercise training on radiation-exposed bone marrow, we evaluated the influence of these physiological host factors on irradiated skeletal muscle morphology and cellular dynamics. Mice were divided into control and high fat diet groups with or without exercise training. All mice were then exposed to radiation and continued in their intervention group for an additional 4 weeks. Diet-induced obesity resulted in increased muscle fibrosis, while obesity and exercise training both increased muscle adiposity. Exercise training enhanced myofibre cross-sectional area and the number of satellite cells committed to the myogenic lineage. High fat groups demonstrated an increase in p-NFĸB expression, a trend for a decline in IL-6 , and increase in TGFB1 . These findings suggest exercise training improves muscle morphology and satellite cell dynamics compared to diet-induced obesity in irradiated muscle, and have implications for exercise interventions in cancer survivors.

Introduction: Radiation therapy increases the risk of secondary malignancy and morbidity in cancer survivors. The role of obesity and exercise training in modulating this risk is not well understood. As such, we used a preclinical model of radiation-induced malignancy to investigate whether diet-induced obesity and/or endurance exercise training altered lifelong survival, cancer incidence, and morbidity. Methods: Male CBA mice were randomly divided into control diet/sedentary group (CTRL/SED), high-fat diet (45% fat)/sedentary group (HFD/SED), control diet/exercise group (2-3 d•wk −1 ; CTRL/EX), or high-fat diet/exercise group (HFD/EX) groups then exposed to whole-body radiation (3 Gy). End point monitoring and pathology determined mortality and cancer incidence, respectively. Health span index, a measure of morbidity, was determined by a composite measure of 10 anthropometric, metabolic, performance, and behavioral measures. Results: Overall survival was higher in HFD/SED compared with CTRL/SED (P < 0.05). The risk of cancer-related mortality by 18 months postradiation was 1.99 and 1.63 in HFD/SED compared with CTRL/EX (RR = 1.99, 95% confidence interval = 1.20-3.31, P = 0.0081) and CTRL/SED (RR = 1.63, 95% confidence interval = 1.06-2.49, P = 0.0250), respectively. The number of mice at end point with cancer was higher in HFD/SED compared with CTRL/EX and CTRL/SED (P < 0.05). Health span index was highest in CTRL/EX (score = +2.5), followed by HFD/EX (score = +1), and HFD/SED (score = −1) relative to CTRL/SED. Conclusion: This work provides the basis for future preclinical studies investigating the dose-response relationship between exercise training and late effects of radiation therapy as well as the mechanisms responsible for these effects.

Weight loss and exercise reduce colorectal cancer (CRC) risk in persons with obesity. Whether weight loss and exercise effect myofibre characteristics and muscle stem/progenitor cell populations in mice with preneoplastic colorectal lesions, a model of CRC risk, is unknown. To address this gap, male C57Bl/6J mice were fed a high-fat diet (HFD) to induce obesity or a control (CON) diet prior to azoxymethane injection to induce preneoplastic colorectal lesions. The HFD group was then randomized to weight loss conditions that included (1) switching to the CON diet only (HFD-SED) or switching to the CON diet with treadmill exercise training (HFD-EX). Average myofibre cross-sectional area was not different between groups. There were more smaller-sized fibers in HFD-EX (p<0.05 vs. CON), and more fibrosis in HFD-SED (p<0.05 vs. HFD-EX and CON). There was a trend for more committed (Pax7+MyoD+) myoblasts (p=0.059) and more fibro-adipogenic progenitors (FAPs) in HFD-EX (p<0.05 vs. CON). Additionally, the canonical pro-inflammatory marker p-NF-κB, was markedly reduced in the insterstitium of HFD-EX (p<0.05 vs. CON and HFD-SED). Our findings suggest that in mice with preneoplastic colorectal lesions, HFD followed by weight loss with exercise, reduces muscle fibrosis and results in a higher content of muscle stem/progenitor cells. Novelty Bullets: • Exercise improves muscle architecture in mice with preneoplastic colorectal lesion • Exercise increases fibro/adipogenic progenitors and reduces inflammatory signaling in mice with preneoplastic colorectal lesions

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Breast cancer accounts for 25% of all cancers among Canadian females. Despite successes of decreased mortality, adverse treatment effects, such as cardiotoxicity, contribute to a sedentary lifestyle and decreased quality of life. Physical activity (PA) is a possible therapy for the late effects; however, COVID-19 restricted access to in-person cardiovascular rehabilitation (CR) programs. The purposes are as follows: (1) compare PA of breast cancer survivors’ in-person CR to virtual CR following a transition during COVID-19 and (2) compare the PA of the pandemic cohort to a matched cohort who had completed the program in 2018/2019; (3) explore survivors’ experiences of transitioning to and engaging in virtual CR. Mixed methods included analysis of CR PA data from a pandemic cohort ( n = 18) and a 2018/2019 cohort ( n = 18) and semi-structured focus group interviews with the pandemic cohort ( n = 9) in the context of the PRECEDE-PROCEED model. After the transition, there were no significant differences in mean activity duration, frequency, and cumulative activity (expressed as MET-minutes) ( p > 0.05). However, variation of PA duration doubled following the transition from in-person to virtual ( p = 0.029), while for the 2018/2019 cohort, variation remained unchanged. Focus groups revealed that women valued their CR experiences pre-COVID-19 and had feelings of anxiety during the transition. Perceived factors affecting participation were environmental, personal, and behavioural. Recommendations for virtual programs were to increase comradery, technology, and professional guidance. PA experiences during a transition to virtual care prompted by a pandemic vary among breast cancer survivors. Targeting individualised strategies and exercise prescriptions are important for improving PA programs and patient outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s00520-022-07142-y.