Exercise During Neoadjuvant Chemoradiation Treatment To Improve Rectal And Esophageal Cancer Outcome (EXENTRO) Pilot Trial

Treatment of patients with high-risk rectal or esophageal cancer mostly consists of neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection. However, nCRT may reduce physical fitness and physical function (PF). Exercise during nCRT might help to maintain physical fitness and PF. In a previous study, we found an improved tumor response in patients with rectal cancer with moderate or high levels of moderate-to-vigorous intensity physical activity at diagnosis (unpublished data). The EXENTRO trial examines feasibility of different exercise programs during nCRT and the preliminary effects on physical fitness, self-reported PF and tumor response. PURPOSE: The present analyses aim to evaluate i) feasibility of a three-arm pilot randomized controlled trial comparing two exercise interventions with similar volume but different type and timing versus usual care in patients with rectal or esophageal cancer during nCRT, and ii) generate preliminary data on exercise effects on physical fitness and PF. METHODS: Prior to nCRT patients were randomized in one of three study arms: 1) two 60 min supervised combined aerobic exercise (AE) and resistance exercise (RE) sessions per week (AE + RE); 2) 30 min AE in-hospital within one hour prior to daily radiotherapy (ExPR), and 3) usual care (UC). Feasibility was assessed in terms of participation rate and adherence, expressed as exercise relative dose intensity (ExRDI). Intervention effects on estimated VO2max (Ästrand-Rhyming test), leg muscle strength (indirect 1 repetition maximum) and PF (SF-36) were analyzed within (paired-samples t-test) and between groups (linear regression models). RESULTS: Currently, 22 of the aimed 39 patients are included with a participation rate of 42%. ExRDI was 66 ± 36% in the AE + RE group vs. 93 ± 6% in the ExPR group. VO2max (-7.7 ± 4.1 ml/kg/min, p = 0.03) and leg muscle strength (-22 ± 13 kg, p = 0.02) decreased during nCRT in the UC group, but not in the intervention groups. The intervention effect on VO2max (β in ml/kg/min = 6.2, 95%CI [0.4 - 12.1], p = 0.04), and PF (β = 30.2, 95%CI [5.5 - 54.9], p = 0.02) was superior in the ExPR group compared to the UC group, but was not different between other groups. CONCLUSION: Both exercise interventions during nCRT are feasible, with the highest adherence in the ExPR group which effectively maintained VO2max and PF. Funded by Hypatia Fellowship grant from Radboudumc to L.B.