title: The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial): study protocol for a randomised controlled trial.
abstract: BACKGROUND
  The standard treatment pathway for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Neoadjuvant CRT has been shown to decrease physical fitness, and this decrease is associated with increased post-operative morbidity. Exercise training can stimulate skeletal muscle adaptations such as increased mitochondrial content and improved oxygen uptake capacity, both of which are contributors to physical fitness. The aims of the EMPOWER trial are to assess the effects of neoadjuvant CRT and an in-hospital exercise training programme on physical fitness, health-related quality of life (HRQoL), and physical activity levels, as well as post-operative morbidity and cancer staging.
  
  
  METHODS
  The EMPOWER Trial is a randomised controlled trial with a planned recruitment of 46 patients with locally advanced rectal cancer and who are undergoing neoadjuvant CRT and surgery. Following completion of the neoadjuvant CRT (week 0) prior to surgery, patients are randomised to an in-hospital exercise training programme (aerobic interval training for 6 to 9 weeks) or a usual care control group (usual care and no formal exercise training). The primary endpoint is oxygen uptake at lactate threshold ([Formula: see text] at [Formula: see text]) measured using cardiopulmonary exercise testing assessed over several time points throughout the study. Secondary endpoints include HRQoL, assessed using semi-structured interviews and questionnaires, and physical activity levels assessed using activity monitors. Exploratory endpoints include post-operative morbidity, assessed using the Post-Operative Morbidity Survey (POMS), and cancer staging, assessed by using magnetic resonance tumour regression grading.
  
  
  CONCLUSIONS
  The EMPOWER trial is the first randomised controlled trial comparing an in-hospital exercise training group with a usual care control group in patients with locally advanced rectal cancer. This trial will allow us to determine whether exercise training following neoadjuvant CRT can improve physical fitness and activity levels, as well as other important clinical outcome measures such as HRQoL and post-operative morbidity. These results will aid the design of a large, multi-centre trial to determine whether an increase in physical fitness improves clinically relevant post-operative outcomes.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01914068 (received: 7 June 2013).
  
  
  BACKGROUND
  University Hospital Southampton NHS Foundation Trust.
authors.affiliation: Anaesthesia and Critical Care Research Area, NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. Lisa.Loughney@uhs.nhs.uk.|Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. Lisa.Loughney@uhs.nhs.uk.
authors.forename: Lisa
authors.initials: L
authors.lastname: Loughney
authors.affiliation: Anaesthesia and Critical Care Research Area, NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. Malcolm.West@uhs.nhs.uk.|Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. Malcolm.West@uhs.nhs.uk.|Academic Unit of Cancer Sciences, Faculty of Medicine, University of Southampton, South Academic Block, Tremona Road, Southampton, SO16 6YD, UK. Malcolm.West@uhs.nhs.uk.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: West
authors.affiliation: Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. g.j.kemp@liverpool.ac.uk.|Department of Musculoskeletal Biology and MRC - Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK. g.j.kemp@liverpool.ac.uk.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Kemp
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK. hrossiter@ucla.edu.|Rehabilitation Clinical Trials Center, Division of Respiratory and Critical Care Physiology and Medicine, Los Angles Biomedical Research Institute, 1124 W Carson St, Torrance, CA, 90502, USA. hrossiter@ucla.edu.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Rossiter
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK. S.Burke@leed.ac.uk.
authors.forename: Shaunna M
authors.initials: SM
authors.lastname: Burke
authors.affiliation: Departments of Molecular and Clinical Cancer Medicine and Biostatistics, University of Liverpool, Liverpool, UK. coxt@liverpool.ac.uk.
authors.forename: Trevor
authors.initials: T
authors.lastname: Cox
authors.affiliation: Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK. chris.barben@aintree.nhs.uk.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Barben
authors.affiliation: Anaesthesia and Critical Care, University College London, London, UK. m.mythen@ucl.ac.uk.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Mythen
authors.affiliation: Institute of Ageing and Chronic Disease, Aintree University Hospital, Liverpool, UK. pmacal@liverpool.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Calverley
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, UK and The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK. palmerd@liverpool.ac.uk.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Palmer
authors.affiliation: Anaesthesia and Critical Care Research Area, NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. M.Grocott@soton.ac.uk.|Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. M.Grocott@soton.ac.uk.
authors.forename: Michael P W
authors.initials: MP
authors.lastname: Grocott
authors.affiliation: Anaesthesia and Critical Care Research Area, NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. Sandy.Jack@uhs.nhs.uk.|Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, CE93, MP24, Tremona Road, Southampton, SO16 6YD, UK. Sandy.Jack@uhs.nhs.uk.
authors.forename: Sandy
authors.initials: S
authors.lastname: Jack
mesh_terms: D059248:Chemoradiotherapy; D002985:Clinical Protocols; D003627:Data Interpretation, Statistical; D005081:Exercise Therapy; D006801:Humans; D017063:Outcome Assessment, Health Care; D010809:Physical Fitness; D011788:Quality of Life; D012004:Rectal Neoplasms / Q000523:psychology / Q000628:therapy*