Exercise Improves Cancer-free Survival and Health Span in a Model of Radiation-induced Cancer

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 a...

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Published in:Medicine and science in sports and exercise 2021-11, Vol.53 (11), p.2254-2263
Main Authors: Farber, Eadan, Kwiecien, Jacek M, Bojic, Dejan, Ngu, Matthew, Akohene-Mensah, Paul, Vanhie, James J, Lloyd, Jessica, Larkin, Jillian, DE Lisio, Michael
Format: Article
Language:English
Subjects:
Animals
Anxiety - prevention & control
Behavior, Animal
Depression - prevention & control
Diet, High-Fat
Disease Models, Animal
Disease-Free Survival
Exercise Therapy
Humans
Male
Mice
Mice, Inbred CBA
Muscle Strength
Neoplasms, Radiation-Induced - complications
Neoplasms, Radiation-Induced - psychology
Neoplasms, Radiation-Induced - rehabilitation
Obesity - complications
Physical Conditioning, Animal - physiology
Sedentary Behavior
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Summary: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. 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. 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. 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.
ISSN:0195-9131
1530-0315
DOI:10.1249/MSS.0000000000002711