title: The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.
abstract: BACKGROUND
  In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness.
  
  
  METHODS
  We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg-1.min-1), and the post-exercise phosphocreatine recovery rate constant (min-1), a measure of muscle mitochondrial capacity in vivo.
  
  
  RESULTS
  Median age was 67 years (IQR 64-75). Differences (95%CI) in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold -2.4 ml.kg-1.min-1 (-3.8, -0.9), p = 0.004; Oxygen uptake at Peak -4.0 ml.kg-1.min-1 (-6.8, -1.1), p = 0.011; and post-exercise phosphocreatine recovery rate constant -0.34 min-1 (-0.51, -0.17), p<0.001.
  
  
  CONCLUSIONS
  The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery.
  
  
  BACKGROUND
  Clinicaltrials.gov registration NCT01859442.
authors.affiliation: Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; 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, United Kingdom; Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, United Kingdom.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: West
authors.affiliation: Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Loughney
authors.affiliation: Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lythgoe
authors.affiliation: Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Barben
authors.affiliation: Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, United Kingdom.
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Adams
authors.affiliation: Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, United Kingdom.
authors.forename: William E
authors.initials: WE
authors.lastname: Bimson
authors.affiliation: Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; 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, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Michael P W
authors.initials: MP
authors.lastname: Grocott
authors.affiliation: Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; 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, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Sandy
authors.initials: S
authors.lastname: Jack
authors.affiliation: 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, United Kingdom; Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, United Kingdom.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Kemp
mesh_terms: D000368:Aged; D059186:Chemoradiotherapy, Adjuvant; D005080:Exercise Test; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000503:physiopathology* / Q000532:radiotherapy; D010085:Oxidative Phosphorylation; D010809:Physical Fitness; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000503:physiopathology* / Q000532:radiotherapy; D006113:United Kingdom