TY - JOUR
T1 - Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer
AU - Brown, Justin C.
AU - Rhim, Andrew D.
AU - Manning, Sara L.
AU - Brennan, Luke
AU - Mansour, Alexandra I.
AU - Rustgi, Anil K.
AU - Damjanov, Nevena
AU - Troxel, Andrea B.
AU - Rickels, Michael R.
AU - Ky, Bonnie
AU - Zemel, Babette S.
AU - Courneya, Kerry S.
AU - Schmitz, Kathryn H.
N1 - Funding Information:
This study was funded by the National Institutes of Health K99-CA218603 (Brown), F31-CA192560 (Brown), R21-CA182767 (Schmitz), U54-CA155850 (Schmitz), and UL1-TR0000003 (Fitzgerald). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2018 Brown et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/10
Y1 - 2018/10
N2 - 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-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-III colon cancer patients randomized into one of three groups: usual-care control, 150 minwk-1 of aerobic exercise (low-dose), and 300 minwk-1 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-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.
AB - 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-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-III colon cancer patients randomized into one of three groups: usual-care control, 150 minwk-1 of aerobic exercise (low-dose), and 300 minwk-1 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-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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U2 - 10.1371/journal.pone.0204875
DO - 10.1371/journal.pone.0204875
M3 - Article
C2 - 30332430
AN - SCOPUS:85055072751
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 10
M1 - e0204875
ER -
