Feasibility and clinical potential of exercise interventions during neoadjuvant chemoradiotherapy in patients with esophageal and rectal cancer

Abstract

Background: Exercise during neoadjuvant chemoradiotherapy (NCRT) has potential to mitigate treatment-related declines in physical fitness, and to improve clinical outcomes, including toxicity and tumor response. However, optimal frequency and timing of exercise remains to be determined. Therefore, this pilot trial aimed to assess feasibility of 2 different exercise interventions during NCRT in patients with esophageal and rectal cancer and to evaluate potential clinical effects.

Methods: Patients were randomized into 1 of 3 study arms during NCRT: (a) 30-min aerobic exercise in-hospital within 1 h prior to each radiotherapy fraction (ExPR), (b) two 60-min supervised combined aerobic and resistance exercise sessions per week (AE + RE), and (c) usual care (UC). Feasibility was assessed by examining participation rate and exercise adherence. Intervention effects on physical fitness, health-related quality of life, treatment-related toxicity, and tumor response in patients with esophageal cancer were explored using regression analyses and 85% confidence intervals (85%CIs).

Results: Thirty-seven patients with esophageal cancer (participation rate = 45%) and 2 patients with rectal cancer (participation rate = 14%) were included. Median session attendance was 98% (interquartile range (IQR): 96%-100%) in the ExPR and 78% (IQR: 33%-100%) in the AE + RE group. We found clinically relevant benefits of exercise on maximal oxygen uptake (VO_2max, mL/kg/min)(ExPR: β = 9.7, 85%CI: 6.9-12.6; AE + RE: β = 5.6, 85%CI: 2.6-8.5) and treatment-related toxicity (ExPR: β = -2.8, 85%CI: -5.4 to -0.2; AE + RE: β = -2.6, 85%CI: -5.3 to 0.0). Additionally, good tumor response was found in 70% in AE + RE and ExPR vs. 55% in UC (odds ratio (OR) = 1.9, 85%CI: 0.5-7.7).

Conclusion: Starting prehabilitation during NCRT is feasible, can increase starting fitness of traditional pre-surgical programs, and has potential to improve clinical outcomes.

Keywords: Aerobic capacity; Esophageal cancer; Exercise intervention; Treatment-related toxicity; Tumor response.

Graphical abstract

Fig. 1

Flowchart of patients with esophageal and rectal cancer included in the EXENTRO trial. EXENTRO = Exercise during Neoadjuvant chemoradiation Treatment to improve esophageal and rectal cancer Outcome.

Fig. 2

Attendance at exercise sessions of patients with esophageal cancer displayed as mean ± SD for (A) the exercise prior to radiotherapy (ExPR) group and (B) the combined aerobic and resistance exercise (AE + RE) group during the 5 weeks of neoadjuvant chemoradiotherapy.

Fig. 3

Results of (A) estimated VO_2max, (B) MSEC, (C) treatment-related toxicity assessed by PRO-CTCAE, and (D) tumor response, displayed for patients with esophageal cancer in the UC group (green), the ExPR group (blue), and the AE + RE group (red). AE + RE = aerobic exercise + resistance exercise; EXENTRO = Exercise during Neoadjuvant chemoradiation Treatment to improve esophageal and rectal cancer Outcome; ExPR = exercise prior to radiotherapy; MSEC = maximal short-time exercise capacity; NCRT = neoadjuvant chemoradiotherapy; PRO-CTCAE = patient-reported version of the Common Terminology Criteria for Adverse Events; UC = usual care; VO_2max = maximal oxygen uptake.