title: The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery.
abstract: BACKGROUND
  Neoadjuvant chemotherapy (NAC) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone. However NAC has adverse effects. We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery.
  
  
  METHODS
  We prospectively studied 116 patients with oesophageal or gastric cancer to assess the effect of NAC on physical fitness, of whom 89 underwent cardiopulmonary exercise testing (CPET) before NAC and proceeded to surgery. 39 patients were tested after all cycles of NAC but prior to surgery. Physical fitness was assessed by measuring oxygen uptake (VO₂ in ml kg(-1) min(-1)) at the estimated lactate threshold (θL) and at peak exercise (VO₂ peak in ml kg(-1) min(-1)).
  
  
  RESULTS
  VO₂ at θL and at peak were significantly lower after NAC compared to pre-NAC values: VO₂ at θL 14.5 ± 3.8 (baseline) vs. 12.3 ± 3.0 (post-NAC) ml kg(-1) min(-1); p ≤ 0.001; VO₂ peak 20.8 ± 6.0 vs. 18.3 ± 5.1 ml kg(-1) min(-1); p ≤ 0.001; absolute VO₂ (ml min(-1)) at θL and peak were also lower post-NAC; p ≤ 0.001. Decreased baseline VO₂ at θL and peak were associated with increased one year mortality in patients who completed a full course of NAC and had surgery; p = 0.014.
  
  
  CONCLUSIONS
  NAC before cancer surgery significantly reduced physical fitness in the overall cohort. Lower baseline fitness was associated with reduced one-year-survival in patients completing NAC and surgery, but not in patients who did not complete NAC. It is possible that in some patients the harms of NAC may outweigh the benefits. Trials Registry Number: NCT01335555.
authors.affiliation: Respiratory Research Group, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool, United Kingdom; Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Road, Southampton, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: s.jack@soton.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Jack
authors.affiliation: Respiratory Research Group, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool, United Kingdom; Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom. Electronic address: mwest@liverpool.ac.uk.
authors.forename: M A
authors.initials: MA
authors.lastname: West
authors.affiliation: Respiratory Research Group, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool, United Kingdom. Electronic address: david.raw@aintree.nhs.uk.
authors.forename: D
authors.initials: D
authors.lastname: Raw
authors.affiliation: Liverpool Hope University, Hope Park, Liverpool, United Kingdom. Electronic address: marwoos@hope.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Marwood
authors.affiliation: Statistical Science, University College London, Torrington Place, London, United Kingdom. Electronic address: g.ambler@ucl.ac.uk.
authors.forename: G
authors.initials: G
authors.lastname: Ambler
authors.affiliation: Respiratory Research Group, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool, United Kingdom. Electronic address: Tristan.cope@aintree.nhs.uk.
authors.forename: T M
authors.initials: TM
authors.lastname: Cope
authors.affiliation: Respiratory Research Group, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool, United Kingdom. Electronic address: milind.shrotri@aintree.nhs.uk.
authors.forename: M
authors.initials: M
authors.lastname: Shrotri
authors.affiliation: Respiratory Research Group, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool, United Kingdom. Electronic address: Richard.sturgess@aintree.nhs.uk.
authors.forename: R P
authors.initials: RP
authors.lastname: Sturgess
authors.affiliation: Respiratory Research Group, Aintree University Hospitals NHS Foundation Trust, Lower Lane, Liverpool, United Kingdom; Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom. Electronic address: pmac@liverpool.ac.uk.
authors.forename: P M A
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: Cancer Sciences Division and Department of Medical Oncology, University Southampton NHS Foundation Trust, Southampton, United Kingdom; NIHR/CR-UK Experimental Cancer Medicine Centre, Southampton, United Kingdom. Electronic address: cho@soton.ac.uk.
authors.forename: C H
authors.initials: CH
authors.lastname: Ottensmeier
authors.affiliation: Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Road, Southampton, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: mike.grocott@soton.ac.uk.
authors.forename: M P W
authors.initials: MP
authors.lastname: Grocott
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010101:Oxygen Consumption; D010809:Physical Fitness; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer surgery; Cardiopulmonary exercise testing; Neoadjuvant chemotherapy; Oesphagogastric; Physical fitness; Survival