Sexual dimorphism modulates the impact of cancer cachexia on lower limb muscle mass and function

doi:10.1016/j.clnu.2011.12.008

Clinical Nutrition

Volume 31, Issue 4, August 2012, Pages 499-505

https://doi.org/10.1016/j.clnu.2011.12.008 Get rights and content

Summary

Background & aims

There is a sparsity of data on the impact of cachexia on human muscle function. This study examined the relationship between cachexia, quality of life and the mass/function/mechanical quality of lower limb skeletal muscle in gastrointestinal cancer patients.

Methods

Quadriceps strength and lower limb power were measured in 54 patients with gastrointestinal cancer (n = 24 ≥ 10% weight-loss) and 18 healthy controls. Quadriceps cross-sectional area was measured in 33/54 patients and in all controls using MRI. Muscle mechanical quality was defined as quadriceps strength/unit quadriceps cross-sectional area. Quality of life was assessed using the EORTC QLQ-C30. Patients with weight-loss ≥10% were classified as cachectic.

Results

In male cachectic patients, quadriceps strength (p = 0.003), lower limb power (p = 0.026), quadriceps cross-sectional area (p = 0.019) and muscle quality (p = 0.008) were reduced compared with controls. In female cachectic patients, quadriceps strength (p = 0.001) and muscle quality (p = 0.001) were reduced compared with controls. Physical function (p = 0.013) and fatigue (p = 0.004) quality of life scores were reduced in male cachectic compared with non-cachectic patients, but not in females.

Conclusions

Muscle quality is reduced in cancer patients. The degree of impairment of lower limb muscle mass, quality and function and the impact on quality of life varies with weight-loss and sex.

Introduction

One third of adults will develop cancer and, in approximately 20% of patients, cachexia will influence adversely duration of survival.¹ Cancer cachexia is usually characterised as a process associated with accelerated loss of skeletal muscle mass, with or without loss of fat mass.² Although muscle wasting is a hallmark of cancer cachexia, there are relatively few data describing regional loss of muscle mass or function in either male or female patients. Muscle loss may have a direct influence on patients’ quality of life as well as a significant impact on treatment tolerance³ and is therefore an important potential therapeutic target.

Lower limb musculature (e.g. the quadriceps) is prone to wasting in patients undergoing prolonged bed rest⁴ and muscle mass correlates with strength in healthy adults.⁵ Therefore, it might be anticipated that cancer patients with loss of muscle mass would have at least a proportionate loss of muscle strength/power. Moreover, if the mechanical quality (MQ), defined as quadriceps strength/unit quadriceps cross-sectional area, also known as relative strength of muscle were reduced, the reduction in function would be proportionately greater. Quadriceps strength has been shown to be reduced in cachectic pancreatic cancer patients.⁶ However, when lower limb extensor strength was normalised to quadriceps cross sectional area (CSA), there was no apparent reduction in muscle MQ.⁶ In contrast, animal models have suggested that the process of cachexia involves selective and early loss of key elements of the contractile structures within skeletal muscle which would likely impact on muscle MQ.⁷ Moreover, ultrastructural analysis has demonstrated myofibrillar disarray, irregular muscle membranes and dystrophic muscle morphology in the muscles of tumour-bearing cachectic animals.⁷

Knowledge of the relationship between muscle mass and function and their potential influence on quality of life in cancer cachexia is limited. The aim of the present study was to characterise regional changes in muscle function in gastrointestinal cancer patients with cachexia. We hypothesized that cancer patients (male and female) with cachexia would have both poorer lower limb muscle strength/function and MQ and that this might impact on quality of life when compared with non-cachectic/low weight-loss (WL) cancer patients or healthy controls (HC).

Section snippets

Participants

Fifty four patients (35 males, mean age 66 yrs, range 39–88 yrs; 19 females, mean age 64 yrs, range 44–83 yrs) with gastrointestinal cancer (oesophageal, gastric, pancreatic, bile duct, rectal) were recruited. All patients were discussed at a regional multidisciplinary meeting and tumour staging was determined either pathologically or radiologically (for those not undergoing surgery) according to the international TNM/UICC classification. There were 5 stage I, 7 stage II, 28 stage III and 14

Demographics

The HC were older than the cancer patients (78 vs 65 yrs, p < 0.001), although the average age of non-cachectic and cachectic patients was similar in both males (mean (range): 68(43–88) years vs 62(39–76) years, respectively, p = 0.130) and females (64(44–76) years vs 63(44–83) years, respectively, p = 0.791). The average WL of cancer patients was 8.4% and all HC were weight-stable. The distribution in site of primary tumour was similar between non-cachectic and cachectic patients (Chi-squared p

Discussion

This study demonstrates that in gastrointestinal cancer patients there is variability in lower limb muscle function, MQ and mass according to the degree of WL and sex. While lower limb muscle mass, strength and power declined in male cancer patients, females appeared to experience attenuated loss of muscle mass and power. MQ was reduced in both male and female cancer patients, but only in females did it decline progressively with cachexia. Such sexual dimorphism extended to the impact of

Statement of authorship

NAS was responsible for patient recruitment, conduct of the study, acquisition and interpretation of data, statistical analysis and manuscript preparation, CG designed the MRI protocol and contributed to image analysis, AJM contributed to image analysis, BHT participated in patient recruitment, IJG contributed to statistical analysis, RJES participated in study design, JAR assisted with study design, KCHF was responsible for the study concept, obtaining approvals and assisted with manuscript

Conflict of interest statement

Each author declared no conflict of financial or personal interests in any company or organisation sponsoring this study.

Author agreement

All authors have made substantial contributions and final approval of the conceptions, drafting, and final version.

Acknowledgements

This project was supported financially by Cancer Research UK (Grant no: C1128/A7309) who had no involvement with study design, data collection or interpretation of data. We acknowledge the contributions of Dr Ian Beggs (Consultant Radiologist, RIE) for facilitating access to the MR facility and for assistance with interpretation of MR images, Lynne Thomson and Claire Malone (Radiographers, RIE) for supervision of MR scanning procedures, the staff of the RIE Clinical Research Facility and we

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^c: KCHF and CAG share senior authorship in this work.

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Original articleSexual dimorphism modulates the impact of cancer cachexia on lower limb muscle mass and function

Summary

Background & aims

Methods

Results

Conclusions

Introduction

Section snippets

Participants

Demographics

Discussion

Statement of authorship

Conflict of interest statement

Author agreement

Acknowledgements

Cancer Cell

Clin Nutr

Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Arch Phys Med Rehabil

Cachexia, survival and the acute phase response

Curr Opin Support Palliat Care

Definition and classification of cancer cachexia: an international consensus

Lancet Oncol

Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity

Clin Cancer Res

Whole muscle contractile parameters and thickness loss during 35-day bed rest

Eur J Appl Physiol

Strength and cross-sectional area of human skeletal muscle

J Physiol

Original article
Sexual dimorphism modulates the impact of cancer cachexia on lower limb muscle mass and function