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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.

West MA, Loughney L, Lythgoe D, Barben CP, Adams VL, Bimson WE, Grocott MP, Jack S, Kemp GJ - PLoS ONE (2014)

Bottom Line: However, the effects of this on physical fitness are unclear.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.This may have implications for targeted interventions to improve physical fitness pre-surgery.

View Article: PubMed Central - PubMed

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.

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.

Conclusion: 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.

Trial registration: Clinicaltrials.gov registration NCT01859442.

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Showing flow of patients through the study protocol.Post-NACRT tests carried out within 48±5 hours of finishing NACRT period.
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pone-0111526-g001: Showing flow of patients through the study protocol.Post-NACRT tests carried out within 48±5 hours of finishing NACRT period.

Mentions: Fifteen patients were eligible for surgery, of which 3 were recruited into a different trial; 12 patients (10 males and 2 females) were recruited and underwent CPET and 31P MRS prior to starting a standardised course of NACRT (Figure 1). All CPETs were carried out 48±5 hours before the 31P MRS scan both at baseline and post-NACRT. All patients underwent CPET and 31P MRS immediately after (post-NACRT) finishing NACRT (at a maximum of 48±5 hours). Table 1 describes baseline patient characteristics and Table 2 describes patient characteristics between baseline and post-NACRT. There were no significant changes in BMI or lung function following NACRT, but there was a small but significant fall in haemoglobin. 83% of diagnosed rectal cancers were T3 with threatened circumferential resection margins.


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.

West MA, Loughney L, Lythgoe D, Barben CP, Adams VL, Bimson WE, Grocott MP, Jack S, Kemp GJ - PLoS ONE (2014)

Showing flow of patients through the study protocol.Post-NACRT tests carried out within 48±5 hours of finishing NACRT period.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257525&req=5

pone-0111526-g001: Showing flow of patients through the study protocol.Post-NACRT tests carried out within 48±5 hours of finishing NACRT period.
Mentions: Fifteen patients were eligible for surgery, of which 3 were recruited into a different trial; 12 patients (10 males and 2 females) were recruited and underwent CPET and 31P MRS prior to starting a standardised course of NACRT (Figure 1). All CPETs were carried out 48±5 hours before the 31P MRS scan both at baseline and post-NACRT. All patients underwent CPET and 31P MRS immediately after (post-NACRT) finishing NACRT (at a maximum of 48±5 hours). Table 1 describes baseline patient characteristics and Table 2 describes patient characteristics between baseline and post-NACRT. There were no significant changes in BMI or lung function following NACRT, but there was a small but significant fall in haemoglobin. 83% of diagnosed rectal cancers were T3 with threatened circumferential resection margins.

Bottom Line: However, the effects of this on physical fitness are unclear.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.This may have implications for targeted interventions to improve physical fitness pre-surgery.

View Article: PubMed Central - PubMed

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.

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.

Conclusion: 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.

Trial registration: Clinicaltrials.gov registration NCT01859442.

Show MeSH
Related in: MedlinePlus