M A West1, L Loughney2, C P Barben3, R Sripadam4, G J Kemp5, M P W Grocott6, S Jack7. 1. 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; Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom. Electronic address: mwest@liverpool.ac.uk. 2. 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. Electronic address: lisa.loughney@uhs.nhs.uk. 3. Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom. Electronic address: chris.barben@aintree.nhs.uk. 4. Clatterbridge Cancer Centre, Wirral, United Kingdom. Electronic address: rajaram.sripadam@ccotrust.nhs.uk. 5. Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom. Electronic address: gkemp@liverpool.ac.uk. 6. Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: mike.grocott@soton.ac.uk. 7. 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. Electronic address: s.jack@soton.ac.uk.
Abstract
BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable locally advanced rectal cancer improves outcome compared with surgery alone. Our primary hypothesis was that NACRT impairs objectively-measured physical fitness. We also wished to explore the relationship between fitness and postoperative outcome. METHOD: In an observational study, we prospectively studied 27 consecutive patients, of whom 25 undertook cardiopulmonary exercise testing (CPET) 2 weeks before and 7 weeks after standardized NACRT, then underwent surgery. In-hospital post-operative morbidity and mortality were recorded. Patients were followed up to 1 year for mortality. Data was analysed blind to clinical details. Receiver-operating characteristic (ROC) analysis defined the predictive value of CPET for in-hospital morbidity at day 5. RESULTS: Oxygen uptake ( [Formula: see text] in ml kg(-1) min(-1)) at estimated lactate threshold (θˆL) and at peak exercise ( [Formula: see text] at peak in ml kg(-1) min(-1)) both significantly decreased post-NACRT: [Formula: see text] at θˆL 12.1 (pre-NACRT) vs. 10.6 (post-NACRT), p < 0.001 (95%CI -1.7, -1.2); [Formula: see text] at peak 18.1 vs. 16.7, p < 0.001 (95%CI -3.1, -1.0). Optimal [Formula: see text] at θˆL and peak pre-NACRT for predicting postoperative morbidity were 12.0 and 18.1 ( [Formula: see text] at θˆL - AUC = 0.71, 77% sensitive and 75% specific; [Formula: see text] at peak - AUC = 0.75, 78% sensitive and 76% specific). Optimal [Formula: see text] at θˆL and peak post-NACRT for predicting postoperative morbidity were 10.7 and 16.7 ( [Formula: see text] at θˆL - AUC = 0.72, 77% sensitive and 83% specific; [Formula: see text] at peak - AUC = 0.80, 85% sensitive and 83% specific). CONCLUSION: NACRT before major rectal cancer surgery significantly decreased physical fitness as assessed by CPET. TRIALS REGISTRY NUMBER: NCT01334593.
BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable locally advanced rectal cancer improves outcome compared with surgery alone. Our primary hypothesis was that NACRT impairs objectively-measured physical fitness. We also wished to explore the relationship between fitness and postoperative outcome. METHOD: In an observational study, we prospectively studied 27 consecutive patients, of whom 25 undertook cardiopulmonary exercise testing (CPET) 2 weeks before and 7 weeks after standardized NACRT, then underwent surgery. In-hospital post-operative morbidity and mortality were recorded. Patients were followed up to 1 year for mortality. Data was analysed blind to clinical details. Receiver-operating characteristic (ROC) analysis defined the predictive value of CPET for in-hospital morbidity at day 5. RESULTS: Oxygen uptake ( [Formula: see text] in ml kg(-1) min(-1)) at estimated lactate threshold (θˆL) and at peak exercise ( [Formula: see text] at peak in ml kg(-1) min(-1)) both significantly decreased post-NACRT: [Formula: see text] at θˆL 12.1 (pre-NACRT) vs. 10.6 (post-NACRT), p < 0.001 (95%CI -1.7, -1.2); [Formula: see text] at peak 18.1 vs. 16.7, p < 0.001 (95%CI -3.1, -1.0). Optimal [Formula: see text] at θˆL and peak pre-NACRT for predicting postoperative morbidity were 12.0 and 18.1 ( [Formula: see text] at θˆL - AUC = 0.71, 77% sensitive and 75% specific; [Formula: see text] at peak - AUC = 0.75, 78% sensitive and 76% specific). Optimal [Formula: see text] at θˆL and peak post-NACRT for predicting postoperative morbidity were 10.7 and 16.7 ( [Formula: see text] at θˆL - AUC = 0.72, 77% sensitive and 83% specific; [Formula: see text] at peak - AUC = 0.80, 85% sensitive and 83% specific). CONCLUSION: NACRT before major rectal cancer surgery significantly decreased physical fitness as assessed by CPET. TRIALS REGISTRY NUMBER: NCT01334593.
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