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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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Related in: MedlinePlus

Averaged number of steps at Baseline (before NACRT)) and at 48±5 hours post-NACRT: lines link data-points (closed circles) for individual patients, and open circles show overall mean±SEM. Mean change (SEM) between baseline and post-NACRT is −1627(712) steps, p = 0.039.
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pone-0111526-g003: Averaged number of steps at Baseline (before NACRT)) and at 48±5 hours post-NACRT: lines link data-points (closed circles) for individual patients, and open circles show overall mean±SEM. Mean change (SEM) between baseline and post-NACRT is −1627(712) steps, p = 0.039.

Mentions: Table 3 shows CPET, PA and 31P MRS-derived variables pre- and post-NACRT. No exercise or MRS adverse events were encountered until end of follow-up. Post-NACRT, there were significant decreases in both absolute (ml.min−1) and relative (ml.kg−1.min−1) o2, in O2 pulse at L and at Peak exercise, in baseline heart rate, in kPCr and in the number of steps (although this is strongly influenced by an apparent outlier; difference in the number of steps was not significant after the outlier was removed); Figure 2 shows mean and individual values of kPCr, o2 at L and o2 at Peak, while Figure 3 shows the mean number of daily steps. E/co2 and work rates at L and Peak exercise did not change. No significant relationship was found between the change in o2 at L and change in haemoglobin (r = 0.27; p = 0.396).


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)

Averaged number of steps at Baseline (before NACRT)) and at 48±5 hours post-NACRT: lines link data-points (closed circles) for individual patients, and open circles show overall mean±SEM. Mean change (SEM) between baseline and post-NACRT is −1627(712) steps, p = 0.039.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111526-g003: Averaged number of steps at Baseline (before NACRT)) and at 48±5 hours post-NACRT: lines link data-points (closed circles) for individual patients, and open circles show overall mean±SEM. Mean change (SEM) between baseline and post-NACRT is −1627(712) steps, p = 0.039.
Mentions: Table 3 shows CPET, PA and 31P MRS-derived variables pre- and post-NACRT. No exercise or MRS adverse events were encountered until end of follow-up. Post-NACRT, there were significant decreases in both absolute (ml.min−1) and relative (ml.kg−1.min−1) o2, in O2 pulse at L and at Peak exercise, in baseline heart rate, in kPCr and in the number of steps (although this is strongly influenced by an apparent outlier; difference in the number of steps was not significant after the outlier was removed); Figure 2 shows mean and individual values of kPCr, o2 at L and o2 at Peak, while Figure 3 shows the mean number of daily steps. E/co2 and work rates at L and Peak exercise did not change. No significant relationship was found between the change in o2 at L and change in haemoglobin (r = 0.27; p = 0.396).

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