BACKGROUND: The Rehabilitation Strategies following Esophagogastric cancer (ReStOre) randomized control trial demonstrated a significant improvement in cardiorespiratory fitness of esophagogastric cancer survivors. This follow-up, exploratory study analyzed the biological effect of exercise intervention on levels of 55 serum proteins, encompassing mediators of angiogenesis, inflammation, and vascular injury, from participants on the ReStOre trial. METHODS: Patients > 6 months disease free from esophagogastric cancer were randomized to usual care or the 12-week ReStOre program (exercise training, dietary counselling, and multidisciplinary education). Serum was collected at baseline (T0), post-intervention (T1), and at 3-month follow up (T2). Serum biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-seven patients participated in this study; 17 in the control arm and 20 in the intervention arm. Exercise intervention resulted in significant alterations in the level of expression of serum IP-10 (mean difference (MD) 38.02 (95% CI 0.69 to 75.35)), IL-27 (MD 249.48 (95% CI 22.43 to 476.53)), and the vascular injury biomarkers, ICAM-1 (MD 1.05 (95% CI 1.07 to 1.66)), and VCAM-1 (MD 1.51 (95% CI 1.04 to 2.14)) at T1. A significant increase in eotaxin-3 (MD 2.59 (95% CI 0.23 to 4.96)), IL-15 (MD 0.27 (95% CI 0 to 0.54)) and decrease in bFGF (MD 1.62 (95% CI -2.99 to 0.26)) expression was observed between control and intervention cohorts at T2 (p < 0.05). CONCLUSIONS: Exercise intervention significantly altered the expression of a number of serum biomarkers in disease-free patients who had prior treatment for esophagogastric cancer. Impact: Exercise rehabilitation causes a significant biological effect on serum biomarkers in esophagogastric cancer survivors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03314311.

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