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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

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
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
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
1932-6203
1-15
West, Malcolm A.
8b5f3c93-86d3-4193-982b-6e45d6223005
Loughney, Lisa
fb9c07ef-a500-41a4-a9cc-871240317ec7
Lythgoe, Daniel
dd33e967-e4a8-4d99-8f6f-a018fcc49614
Barben, Christopher P.
d069bada-b39e-4d07-95b2-d45fd84037b8
Adams, Valerie L.
8be1de77-88ae-4045-8c44-cb58134091b1
Bimson, William E.
793154ab-3df6-47bb-b272-384f62920abc
Grocott, Michael P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Jack, Sandy
3275b6b3-9f60-4901-9b2f-b03aab101638
Kemp, Graham J.
e655122f-ff43-49ae-92d3-b569d4cb7707
West, Malcolm A.
8b5f3c93-86d3-4193-982b-6e45d6223005
Loughney, Lisa
fb9c07ef-a500-41a4-a9cc-871240317ec7
Lythgoe, Daniel
dd33e967-e4a8-4d99-8f6f-a018fcc49614
Barben, Christopher P.
d069bada-b39e-4d07-95b2-d45fd84037b8
Adams, Valerie L.
8be1de77-88ae-4045-8c44-cb58134091b1
Bimson, William E.
793154ab-3df6-47bb-b272-384f62920abc
Grocott, Michael P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Jack, Sandy
3275b6b3-9f60-4901-9b2f-b03aab101638
Kemp, Graham J.
e655122f-ff43-49ae-92d3-b569d4cb7707

West, Malcolm A., Loughney, Lisa, Lythgoe, Daniel, Barben, Christopher P., Adams, Valerie L., Bimson, William E., Grocott, Michael P.W., Jack, Sandy and Kemp, Graham J. (2014) 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 PLoS ONE, 9, (12), pp. 1-15. (doi:10.1371/journal.pone.0111526). (PMID:17440956).

Record type: Article

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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Published date: 5 December 2014
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 372854
URI: http://eprints.soton.ac.uk/id/eprint/372854
ISSN: 1932-6203
PURE UUID: 86b48f01-4829-487f-be87-2948bbc1220c

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Date deposited: 23 Dec 2014 14:51
Last modified: 17 Jul 2017 21:38

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Contributors

Author: Malcolm A. West
Author: Lisa Loughney
Author: Daniel Lythgoe
Author: Christopher P. Barben
Author: Valerie L. Adams
Author: William E. Bimson
Author: Sandy Jack
Author: Graham J. Kemp

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