Effect of the Rehabilitation Program, ReStOre, on Serum Biomarkers in a Randomized Control Trial of Esophagogastric Cancer Survivors

Susan A Kennedy; Stephanie L Annett; Margaret R Dunne; Fiona Boland; Linda M O'Neill; Emer M Guinan; Suzanne L Doyle; Emma K Foley; Jessie A Elliott; Conor F Murphy; Annemarie E Bennett; Michelle Carey; Daniel Hillary; Tracy Robson; John V Reynolds; Juliette Hussey; Jacintha O'Sullivan

doi:10.3389/fonc.2021.669078

Effect of the Rehabilitation Program, ReStOre, on Serum Biomarkers in a Randomized Control Trial of Esophagogastric Cancer Survivors

Front Oncol. 2021 Sep 15:11:669078. doi: 10.3389/fonc.2021.669078. eCollection 2021.

Authors

Susan A Kennedy¹, Stephanie L Annett², Margaret R Dunne¹, Fiona Boland³, Linda M O'Neill⁴, Emer M Guinan⁵, Suzanne L Doyle⁶, Emma K Foley¹, Jessie A Elliott¹, Conor F Murphy¹, Annemarie E Bennett⁴, Michelle Carey⁷, Daniel Hillary⁷, Tracy Robson², John V Reynolds¹, Juliette Hussey⁴, Jacintha O'Sullivan¹

Affiliations

¹ Trinity St. James's Cancer Institute, Trinity Translational Medicine Institute, Department of Surgery, St. James's Hospital, Trinity College Dublin, Dublin, Ireland.
² School of Pharmacy and Biomolecular Science, Royal College of Surgeons Ireland, Dublin, Ireland.
³ Data Science Centre, Royal College of Surgeons Ireland, Dublin, Ireland.
⁴ Discipline of Physiotherapy, School of Medicine, Trinity College Dublin, Dublin, Ireland.
⁵ School of Medicine, Trinity College Dublin, Dublin, Ireland.
⁶ School of Biological Sciences, Dublin Institute of Technology, Dublin, Ireland.
⁷ School of Mathematics & Statistics, University College Dublin, Dublin, Ireland.

Abstract

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).

Keywords: biomarker analysis; cancer rehabilitation; cancer survivorship; cardiorespiratory fitness; esophagogastric cancer; exercise training; multidisciplinary rehabilitation treatment.

Associated data

ClinicalTrials.gov/NCT03314311