The high rate of recurrent disease is a critical barrier to promote the health and longevity of colon cancer (CC) survivors. An approach to reduce this barrier is to develop interventions to minimize recurrence that CC survivors can accomplish autonomously, such as lifestyle and behavioral modification. Epidemiologic evidence suggests that increasing levels of post-diagnosis physical activity is associated with a 42% improvement in disease-free survival, 40% reduction in recurrence, and 45-71% reduction in CC-specific mortality. However, the underlying molecular mechanisms of this association remain unidentified. Characterizing biomarkers that promote existing tumor growth and dissemination of circulating tumor cells (CTCs) may advance knowledge of CC recurrence and progression. Cell-adhesion molecules play a pivotal role in the development and progression of CC recurrence. Cell-adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular adhesion molecule-1 (sVCAM-1), promote the growth and progression of existing micro-metastases, and promote the formation of additional metastatic foci by enabling CTC invasion of the extracellular matrix, infiltration and dissemination throughout the blood stream, and extravasation into distant organs. This pilot study will randomize 39 CC survivors to three equal-sized groups: low dose (150 min?wk-1) moderate-intensity aerobic exercise, high-dose (300 min?wk-1) moderate-intensity aerobic exercise, or a control group, for 26-weeks. Participants will be provided with in-home treadmills to support the achievement of these exercise goals. Our research team has demonstrated success in prescribing these volumes of aerobic exercise. The primary aims of this trial are to quantify and describe the feasibility, incidence of healthcare events requiring dose-reduction or cessation of exercise and to gather preliminary evidence regarding the biologic efficacy of two distinct doses of aerobic exercise on two cell-adhesion biomarkers associated with CC recurrence and metastasis (sICAM-1 and sVCAM-1). We will then explore the relationship between cell-adhesion molecules and CTCs. This line of investigation aligns with the current mission of the National Cancer Institute PAR-12-229, and provocative question PQA-5, which aim to elucidate the optimal exercise prescription to improve molecular pathways hypothesized to underlie the association between physical activity and cancer prognosis.

Public Health Relevance

Despite the success of surgery and chemotherapy among people with colon cancer (CC), 30-50% of patients develop recurrent disease. Physical activity has emerged as a potential lifestyle intervention to reduce cancer recurrence and improve survival among people with CC. This pilot study aims to identify the dose-response effects of exercise on molecular and cellular pathways associated with physical activity and CC outcomes.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-PSE-K (57))
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Alfano, Catherine M
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University of Pennsylvania
Biostatistics & Other Math Sci
Schools of Medicine
United States
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Brown, Justin C; Troxel, Andrea B; Ky, Bonnie et al. (2016) A randomized phase II dose-response exercise trial among colon cancer survivors: Purpose, study design, methods, and recruitment results. Contemp Clin Trials 47:366-75
Brown, Justin C; Kontos, Despina; Schnall, Mitchell D et al. (2016) The Dose-Response Effects of Aerobic Exercise on Body Composition and Breast Tissue among Women at High Risk for Breast Cancer: A Randomized Trial. Cancer Prev Res (Phila) 9:581-8
Rogers, Benjamin H; Brown, Justin C; Gater, David R et al. (2016) Association Between Maximal Bench Press Strength and Isometric Handgrip Strength Among Breast Cancer Survivors. Arch Phys Med Rehabil :
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2016) Anthropometrically-predicted visceral adipose tissue and mortality among men and women in the third national health and nutrition examination survey (NHANES III). Am J Hum Biol :
Brown, J C; Harhay, M O; Harhay, M N (2016) Visceral adipose tissue dysfunction and mortality among a population-based sample of males and females. Diabetes Metab 42:382-385
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2016) Patient-reported versus objectively-measured physical function and mortality risk among cancer survivors. J Geriatr Oncol 7:108-15
Brown, Justin C; Schmitz, Kathryn H (2015) Weight lifting and appendicular skeletal muscle mass among breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat 151:385-92
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2015) The Prognostic Importance of Frailty in Cancer Survivors. J Am Geriatr Soc 63:2538-2543
Brown, Justin C; Ko, Emily M; Schmitz, Kathryn H (2015) Development of a risk-screening tool for cancer survivors to participate in unsupervised moderate- to vigorous-intensity exercise: results from a survey study. PM R 7:113-22
Brown, J C; Harhay, M O; Harhay, M N (2015) Physical function as a prognostic biomarker among cancer survivors. Br J Cancer 112:194-8

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