Date of Award
Doctor of Philosophy (PhD)
Epidemiology & Biostatistics
Kathryn H. Schmitz
Observational epidemiologic data suggest that participation in physical activity after a diagnosis of colon cancer reduces the risk of cancer recurrence, cancer-specific mortality, and all-cause mortality. However, the biologic mechanisms that mediate the relationship between physical activity and disease outcomes among colon cancer survivors have not been characterized. Excess visceral adipose tissue and hyperinsulinemia promote the growth and progression of existing micro-metastases and the development of new distant metastases. Exercise reduces visceral adipose tissue and hyperinsulinemia among non-diabetic persons with obesity. However, it is unknown if exercise alters visceral adipose tissue and hyperinsulinemia among colon cancer survivors. We conducted a phase II, randomized, six month, dose-response exercise trial that compared 150 min•wk-1 or 300 min•wk-1 of moderate-intensity aerobic exercise to a usual care control group among 39 colon cancer survivors. We examined the efficacy of exercise to reduce visceral adipose tissue and fasting insulin. To understand the generalizability of this trial we examined demographic, clinical, and geographic characteristics of trial participants as compared to the cancer registry population from which they were recruited. Mean age was 56.5±10.0 years, 51% had stage III disease, 72% were treated with chemotherapy, and the mean time since finishing treatment was 10.9±6.1 months. Over six months, the low-dose group completed 141.5±9.9 min∙wk-1 of aerobic exercise, and the high-dose group completed 247.2±10.7 min∙wk-1 of aerobic exercise. VAT increased 5.31±4.80 cm2 in the control group, and decreased 4.13±4.53 in the low-dose group, and 8.27±4.89 in the high-dose group (linear Ptrend=0.008). Fasting insulin concentrations decreased 7.4±9.4 pmol/L in the control group, 28.0±8.3 pmol/L in the low-dose group, and 20.7±9.3 pmol/L in the high-dose group (nonlinear Ptrend=0.042). Colon cancer survivors screened for eligibility and enrolled in the study were younger (screening P<0.001, enrollment P=0.007) and more likely to have been treated with chemotherapy (screening P<0.001, enrollment P=0.006) than the population from which they were recruited. The findings from this trial inform key design aspects for future phase II and phase III randomized controlled trials among colon cancer survivors.
Brown, Justin Charles, "The Courage Trial: A Phase II Randomized Clinical Trial to Evaluate the Dose-Response Effects of Exercise on Prognostic Biomarkers Among Colon Cancer Survivors" (2016). Publicly Accessible Penn Dissertations. 1625.