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Grant Details

Grant Number: 5R21CA182767-02 Interpret this number
Primary Investigator: Schmitz, Kathryn
Organization: University Of Pennsylvania
Project Title: The Courage Trial: Colon Recurrence and Aerobic Exercise: a Feasibility Study
Fiscal Year: 2015


Abstract

DESCRIPTION (provided by applicant): 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.



Publications

Applying pre-participation exercise screening to breast cancer survivors: a cross-sectional study.
Authors: Igwebuike L.T. , Zhang X. , Brown J.C. , Schmitz K.H. .
Source: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2018 Jun; 26(6), p. 1825-1831.
EPub date: 2017-12-19.
PMID: 29260391
Related Citations

A randomized dose-response trial of aerobic exercise and health-related quality of life in colon cancer survivors.
Authors: Brown J.C. , Damjanov N. , Courneya K.S. , Troxel A.B. , Zemel B.S. , Rickels M.R. , Ky B. , Rhim A.D. , Rustgi A.K. , Schmitz K.H. .
Source: Psycho-oncology, 2018 04; 27(4), p. 1221-1228.
EPub date: 2018-02-20.
PMID: 29388275
Related Citations

Dose-response Effects of Aerobic Exercise Among Colon Cancer Survivors: A Randomized Phase II Trial.
Authors: Brown J.C. , Troxel A.B. , Ky B. , Damjanov N. , Zemel B.S. , Rickels M.R. , Rhim A.D. , Rustgi A.K. , Courneya K.S. , Schmitz K.H. .
Source: Clinical colorectal cancer, 2018 03; 17(1), p. 32-40.
EPub date: 2017-06-17.
PMID: 28669606
Related Citations

Anthropometrically predicted visceral adipose tissue and blood-based biomarkers: a cross-sectional analysis.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: European journal of nutrition, 2018 Feb; 57(1), p. 191-198.
EPub date: 2016-09-10.
PMID: 27614626
Related Citations

Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer.
Authors: Brown J.C. , Rhim A.D. , Manning S.L. , Brennan L. , Mansour A.I. , Rustgi A.K. , Damjanov N. , Troxel A.B. , Rickels M.R. , Ky B. , et al. .
Source: PloS one, 2018; 13(10), p. e0204875.
EPub date: 2018-10-17.
PMID: 30332430
Related Citations

Dose-response effects of exercise on insulin among colon cancer survivors.
Authors: Brown J.C. , Rickels M.R. , Troxel A.B. , Zemel B.S. , Damjanov N. , Ky B. , Rhim A.D. , Rustgi A.K. , Courneya K.S. , Schmitz K.H. .
Source: Endocrine-related cancer, 2018 01; 25(1), p. 11-19.
EPub date: 2017-10-10.
PMID: 29018055
Related Citations

Dose-response effects of aerobic exercise on body composition among colon cancer survivors: a randomised controlled trial.
Authors: Brown J.C. , Zemel B.S. , Troxel A.B. , Rickels M.R. , Damjanov N. , Ky B. , Rhim A.D. , Rustgi A.K. , Courneya K.S. , Schmitz K.H. .
Source: British journal of cancer, 2017-11-21; 117(11), p. 1614-1620.
EPub date: 2017-09-21.
PMID: 28934762
Related Citations

The dose-response effects of aerobic exercise on musculoskeletal injury: a post hoc analysis of a randomized trial.
Authors: Brown J.C. , Schmitz K.H. .
Source: Research in sports medicine (Print), 2017 Jul-Sep; 25(3), p. 277-289.
EPub date: 2017-04-06.
PMID: 28385043
Related Citations

Nonalcoholic fatty liver disease and mortality among cancer survivors.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: Cancer epidemiology, 2017 06; 48, p. 104-109.
EPub date: 2017-04-29.
PMID: 28460349
Related Citations

Association Between Maximal Bench Press Strength and Isometric Handgrip Strength Among Breast Cancer Survivors.
Authors: Rogers B.H. , Brown J.C. , Gater D.R. , Schmitz K.H. .
Source: Archives of physical medicine and rehabilitation, 2017 02; 98(2), p. 264-269.
EPub date: 2016-08-16.
PMID: 27543047
Related Citations

Anthropometrically-predicted visceral adipose tissue and mortality among men and women in the third national health and nutrition examination survey (NHANES III).
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: American journal of human biology : the official journal of the Human Biology Council, 2017 Jan; 29(1), .
EPub date: 2016-07-17.
PMID: 27427402
Related Citations

Obesity and Energy Balance in GI Cancer.
Authors: Brown J.C. , Meyerhardt J.A. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016-12-10; 34(35), p. 4217-4224.
EPub date: 2016-11-07.
PMID: 27903148
Related Citations

Visceral adipose tissue dysfunction and mortality among a population-based sample of males and females.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: Diabetes & metabolism, 2016 Nov; 42(5), p. 382-385.
EPub date: 2016-06-06.
PMID: 27283873
Related Citations

The Dose-Response Effects of Aerobic Exercise on Body Composition and Breast Tissue among Women at High Risk for Breast Cancer: A Randomized Trial.
Authors: Brown J.C. , Kontos D. , Schnall M.D. , Wu S. , Schmitz K.H. .
Source: Cancer prevention research (Philadelphia, Pa.), 2016 Jul; 9(7), p. 581-8.
EPub date: 2016-04-20.
PMID: 27099272
Related Citations

A randomized phase II dose-response exercise trial among colon cancer survivors: Purpose, study design, methods, and recruitment results.
Authors: Brown J.C. , Troxel A.B. , Ky B. , Damjanov N. , Zemel B.S. , Rickels M.R. , Rhim A.D. , Rustgi A.K. , Courneya K.S. , Schmitz K.H. .
Source: Contemporary clinical trials, 2016 Mar; 47, p. 366-75.
EPub date: 2016-03-10.
PMID: 26970181
Related Citations

Patient-reported versus objectively-measured physical function and mortality risk among cancer survivors.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: Journal of geriatric oncology, 2016 Mar; 7(2), p. 108-15.
EPub date: 2016-02-18.
PMID: 26907563
Related Citations

The Prognostic Importance of Frailty in Cancer Survivors.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: Journal of the American Geriatrics Society, 2015 Dec; 63(12), p. 2538-2543.
EPub date: 2015-11-14.
PMID: 26566767
Related Citations

Weight lifting and appendicular skeletal muscle mass among breast cancer survivors: a randomized controlled trial.
Authors: Brown J.C. , Schmitz K.H. .
Source: Breast cancer research and treatment, 2015 Jun; 151(2), p. 385-92.
EPub date: 2015-05-03.
PMID: 25935584
Related Citations

Development of a risk-screening tool for cancer survivors to participate in unsupervised moderate- to vigorous-intensity exercise: results from a survey study.
Authors: Brown J.C. , Ko E.M. , Schmitz K.H. .
Source: PM & R : the journal of injury, function, and rehabilitation, 2015 Feb; 7(2), p. 113-22.
EPub date: 2014-09-10.
PMID: 25217819
Related Citations

Physical function as a prognostic biomarker among cancer survivors.
Authors: Brown J.C. , Harhay M.O. , Harhay M.N. .
Source: British journal of cancer, 2015-01-06; 112(1), p. 194-8.
EPub date: 2014-11-13.
PMID: 25393366
Related Citations

The prescription or proscription of exercise in colorectal cancer care.
Authors: Brown J.C. , Schmitz K.H. .
Source: Medicine and science in sports and exercise, 2014 Dec; 46(12), p. 2202-9.
PMID: 24781887
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