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The dose-response effect of aerobic exercise on inflammation in colon cancer survivors
Brown JC, Compton SLE, Meyerhardt JA, Spielmann G, Yang S
Frontiers in Oncology 2023 Dec 12;13(1257767):Epub
clinical trial
7/10 [Eligibility criteria: No; Random allocation: Yes; Concealed allocation: No; Baseline comparability: Yes; Blind subjects: No; Blind therapists: No; Blind assessors: Yes; Adequate follow-up: Yes; Intention-to-treat analysis: Yes; Between-group comparisons: Yes; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed*

BACKGROUND: Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. METHODS: In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFalphaR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage. RESULTS: In the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFalphaR2. Cancer stage modified the association between randomized group and hs-CRP (p = 0.022) and IL6 (p < 0.001) but not sTNFalphaR2 (p = 0.39). In stage I to II disease, compared to control, exercise was not associated with inflammation outcomes. In stage III disease, compared to control, low-dose exercise reduced hs-CRP: -35.4% (95% CI -70.1 to -0.7) and IL6: -29.6% (95% CI -58.4 to -0.8) but not sTNFalphaR2: 2.7% (95% CI sTNFalphaR2 -15.7 to 21.1); high-dose exercise was not associated with inflammation outcomes in stage III disease. CONCLUSION: This exploratory analysis offers preliminary data to support the hypothesis that inflammation may mediate the association between physical activity and disease-free survival in colon cancer. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT02250053.

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