Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer

Justin C. Brown, Andrew D. Rhim, Sara L. Manning, Luke Brennan, Alexandra I. Mansour, Anil K. Rustgi, Nevena Damjanov, Andrea B. Troxel, Michael R. Rickels, Bonnie Ky, Babette S. Zemel, Kerry S. Courneya, Kathryn Schmitz

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Abstract

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.

Original languageEnglish (US)
Article numbere0204875
JournalPloS one
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2018

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Circulating Neoplastic Cells
colorectal neoplasms
Colonic Neoplasms
Tumors
exercise
Cells
Exercise
Insulin
relapse
dosage
Histology
physical activity
body mass index
Microfluidics
insulin
Statistical methods
Blood
Tissue
Body Mass Index
Antibodies

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Brown, J. C., Rhim, A. D., Manning, S. L., Brennan, L., Mansour, A. I., Rustgi, A. K., ... Schmitz, K. (2018). Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer. PloS one, 13(10), [e0204875]. https://doi.org/10.1371/journal.pone.0204875
Brown, Justin C. ; Rhim, Andrew D. ; Manning, Sara L. ; Brennan, Luke ; Mansour, Alexandra I. ; Rustgi, Anil K. ; Damjanov, Nevena ; Troxel, Andrea B. ; Rickels, Michael R. ; Ky, Bonnie ; Zemel, Babette S. ; Courneya, Kerry S. ; Schmitz, Kathryn. / Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer. In: PloS one. 2018 ; Vol. 13, No. 10.
@article{d7ad85be46e841e3830a39558ba7d104,
title = "Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer",
abstract = "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.",
author = "Brown, {Justin C.} and Rhim, {Andrew D.} and Manning, {Sara L.} and Luke Brennan and Mansour, {Alexandra I.} and Rustgi, {Anil K.} and Nevena Damjanov and Troxel, {Andrea B.} and Rickels, {Michael R.} and Bonnie Ky and Zemel, {Babette S.} and Courneya, {Kerry S.} and Kathryn Schmitz",
year = "2018",
month = "10",
day = "1",
doi = "10.1371/journal.pone.0204875",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

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, K 2018, 'Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer', PloS one, vol. 13, no. 10, e0204875. https://doi.org/10.1371/journal.pone.0204875

Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer. / Brown, Justin C.; Rhim, Andrew D.; Manning, Sara L.; Brennan, Luke; Mansour, Alexandra I.; Rustgi, Anil K.; Damjanov, Nevena; Troxel, Andrea B.; Rickels, Michael R.; Ky, Bonnie; Zemel, Babette S.; Courneya, Kerry S.; Schmitz, Kathryn.

In: PloS one, Vol. 13, No. 10, e0204875, 01.10.2018.

Research output: Contribution to journalArticle

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

PY - 2018/10/1

Y1 - 2018/10/1

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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Brown JC, Rhim AD, Manning SL, Brennan L, Mansour AI, Rustgi AK et al. Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer. PloS one. 2018 Oct 1;13(10). e0204875. https://doi.org/10.1371/journal.pone.0204875