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Effects of exercise on circulating tumor cells among patients with resected stage I to III colon cancer
Brown JC, Rhim AD, Manning SL, Brennan L, Mansour AI, Rustgi AK, Damjanov N, Troxel AB, Rickels MR, Ky B, Zemel BS, Courneya KS, Schmitz KH
PLoS ONE 2018 Oct;13(10):e0204875
clinical trial
4/10 [Eligibility criteria: No; Random allocation: Yes; Concealed allocation: No; Baseline comparability: Yes; Blind subjects: No; Blind therapists: No; Blind assessors: Yes; Adequate follow-up: No; Intention-to-treat analysis: No; Between-group comparisons: No; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed*

BACKGROUND: Physical activity is associated with a lower risk of disease recurrence among colon cancer patients. Circulating tumor cells (CTC) are prognostic of disease recurrence among stage I to III colon cancer patients. The pathways through which physical activity may alter disease outcomes are unknown, but may be mediated by changes in CTCs. METHODS: Participants included 23 stage I to III colon cancer patients randomized into one of three groups: usual-care control, 150 min/wk of aerobic exercise (low-dose), and 300 min/wk of aerobic exercise (high-dose) for six months. CTCs from venous blood were quantified in a blinded fashion using an established microfluidic antibody-mediated capture device. Poisson regression models estimated the logarithmic counts of CTCs. RESULTS: At baseline, 78% (18/23) of patients had >= 1 CTC. At baseline, older age (-0.12 +/- 0.06; p = 0.04), lymphovascular invasion (0.63 +/- 0.25; p = 0.012), moderate/poor histology (1.09 +/- 0.34; p = 0.001), body mass index (0.07 +/- 0.02; p = 0.001), visceral adipose tissue (0.08 +/- 0.04; p = 0.036), insulin (0.06 +/- 0.02; p = 0.011), sICAM-1 (0.04 +/- 0.02; p = 0.037), and sVCAM-1 (0.06 +/- 0.03; p = 0.045) were associated with CTCs. Over six months, significant decreases in CTCs were observed in the low-dose (-1.34 +/- 0.34; p < 0.001) and high-dose (-1.18 +/- 0.40; p = 0.004) exercise groups, whereas no significant change was observed in the control group (-0.59 +/- 0.56; p = 0.292). Over six months, reductions in body mass index (-0.07 +/- 0.02; p = 0.007), insulin (-0.08 +/- 0.03; p = 0.014), and sICAM-1 (-0.07 +/- 0.03; p = 0.005) were associated with reductions in CTCs. The main limitations of this proof-of-concept study are the small sample size, heterogenous population, and per-protocol statistical analysis. CONCLUSION: Exercise may reduce CTCs among stage I to III colon cancer patients. Changes in host factors correlated with changes in CTCs. Exercise may have a direct effect on CTCs and indirect effects through alterations in host factors. This hypothesis-generating observation derived from a small pilot study warrants further investigation and replication.

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