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

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 min∙wk-1 of aerobic exercise (low-dose), and 300 min∙wk-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.

研究背景
体力活动与结肠癌患者的疾病复发风险降低存在关联。循环肿瘤细胞（circulating tumor cells, CTC）可作为I-III期结肠癌患者疾病复发的预后标志物。目前尚不清楚体力活动影响疾病转归的具体通路，但该效应或可通过循环肿瘤细胞的变化介导。

研究方法
本研究纳入23例I-III期结肠癌患者，将其随机分为三组：常规护理对照组、每周150分钟有氧运动（低剂量组）以及每周300分钟有氧运动（高剂量组），干预时长为6个月。采用经验证的微流控抗体介导捕获装置，以盲法对静脉血中的循环肿瘤细胞进行定量检测。通过泊松回归模型估算循环肿瘤细胞的对数计数。

研究结果
基线时，78%（18/23）的患者检出至少1个循环肿瘤细胞。基线分析显示，年龄较大（−0.12±0.06；P=0.04）、脉管癌栓阳性（0.63±0.25；P=0.012）、组织学分级为中/低分化（1.09±0.34；P=0.001）、体质量指数（0.07±0.02；P=0.001）、内脏脂肪组织含量（0.08±0.04；P=0.036）、胰岛素水平（0.06±0.02；P=0.011）、可溶性细胞间黏附分子1（sICAM-1，0.04±0.02；P=0.037）以及可溶性血管细胞黏附分子1（sVCAM-1，0.06±0.03；P=0.045）均与循环肿瘤细胞水平相关。干预6个月后，低剂量运动组（−1.34±0.34；P<0.001）与高剂量运动组（−1.18±0.40；P=0.004）的循环肿瘤细胞水平均出现显著降低，而对照组未观察到显著变化（−0.59±0.56；P=0.292）。干预6个月期间，体质量指数（−0.07±0.02；P=0.007）、胰岛素水平（−0.08±0.03；P=0.014）以及可溶性细胞间黏附分子1（−0.07±0.03；P=0.005）的降低与循环肿瘤细胞水平的降低相关。本概念验证研究的主要局限性包括样本量较小、人群异质性较高以及采用符合方案的统计分析。

研究结论
有氧运动可降低I-III期结肠癌患者的循环肿瘤细胞水平。宿主因素的变化与循环肿瘤细胞水平的变化存在相关性。有氧运动可能对循环肿瘤细胞产生直接作用，也可通过改变宿主因素发挥间接影响。这项源自小型预试验的假说生成性观察结果，有待进一步的研究验证与重复。