Structured exercise during neo-adjuvant chemotherapy in patients with operable adenocarcinoma of the oesophagus and gastro-oesophageal junction

Abstract

Neo-adjuvant chemotherapy (NAC) results in physical deconditioning prior to high-risk surgery in patients diagnosed with oesophageal adenocarcinoma but remains the gold standard of care for patients with operable disease. Overall, physical and mental decline has been reported in patients, with a delayed return to baseline health-related quality of life (HRQL) following treatment. Exercise has been shown to improve fitness in patients undergoing non-cancer elective surgery. Furthermore, improved cancer control and immune function has been reported in exercising mice under laboratory conditions. Aim: The aim of this thesis is to examine the feasibility of a structured exercise prehabilitation program commencing prior to chemotherapy and continuing during treatment and the impact on outcomes for cancer patients. Methods: Patients were invited to participate in a clinical trial of exercise prehabilitation concomitant with standard care versus standard care alone. Following informed and written consent, patients were enrolled into the Pre-EMPT study and clinical data collection commenced. Post-operative tumour histopathology assessment was carried out according to Royal College of Pathology guidelines. Cardiopulmonary exercise testing was performed during treatment. CT scans were assessed for body composition changes post-NAC. Immunity and Inflammatory bloods were assessed. HRQL was measured using validated patient reported outcomes. Results: A decline in patient fitness following NAC, measured by VO2peak, was blunted by 7% in patients undergoing the structured exercise prehabilitation program (-19% Control vs -12% Intervention). Overall length of hospital stay was lower than the national average in both groups, as were post-operative complications. Improved cancer control was evident in the Intervention group, measured by pathological evidence of disease regression in both primary tumour and lymph nodes. There was reversal of sarcopenic obesity with improved visceral /subcutaneous fat ratios in patients undergoing exercise prehabilitation. In addition, immune function was significantly improved with greater regulation of inflammatory markers (i.e. Interleukin-6). Overall mental wellbeing, measured using the Shortened Warwick-Edinburgh Mental Well-Being Scale, was less perturbed in the Intervention group, also showing a recovery to baseline at 12 months after surgery. Conclusions: A structured exercise prehabilitation program during neo-adjuvant chemotherapy and prior to surgery is feasible and beneficial to patients with operable oesophageal adenocarcinoma. A structured exercise intervention reduces physical decline and improves cancer control in patients undergoing NAC.