Muscle mass as a target to reduce fatigue in patients with advanced cancer

Elisabeth C W Neefjes, Renske M van den Hurk, Susanne Blauwhoff-Buskermolen, Maurice J D L van der Vorst, Annemarie Becker-Commissaris, Marian A E de van der Schueren, Laurien M Buffart, Henk M W Verheul, Elisabeth C W Neefjes, Renske M van den Hurk, Susanne Blauwhoff-Buskermolen, Maurice J D L van der Vorst, Annemarie Becker-Commissaris, Marian A E de van der Schueren, Laurien M Buffart, Henk M W Verheul

Abstract

Background: Cancer-related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF.

Methods: A total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-fatigue questionnaire (cut-off for fatigue <34). Multiple linear regression analyses were conducted to study the association between SMI and CRF adjusting for relevant confounders.

Results: In this group of patients with advanced cancer, the median fatigue score was 36 (interquartile range 26-44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B - 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy-fatigue score was found (n = 82).

Conclusions: The association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies.

Keywords: Cancer; Exercise; Fatigue; Muscle; Neoplasms.

© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
Correlation of skeletal muscle index (SMI) and Functional Assessment of Chronic Illness Therapy (FACIT)‐fatigue.

References

    1. Berger A. Cancer‐related fatigue NCCN guidelines. 2015. 22‐1‐2015.
    1. Hofman M, Ryan JL, Figueroa‐Moseley CD, Jean‐Pierre P, Morrow GR. Cancer‐related fatigue: the scale of the problem. Oncologist 2007;12:4–10.
    1. Servaes P, Verhagen C, Bleijenberg G. Fatigue in cancer patients during and after treatment: prevalence, correlates and interventions. Eur J Cancer 2002;38:27–43.
    1. Neefjes EC, van der Vorst MJ, Blauwhoff‐Buskermolen S, Verheul HM. Aiming for a better understanding and management of cancer‐related fatigue. Oncologist 2013;18:1135–1143.
    1. Bower JE. Cancer‐related fatigue—mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 2014;11:597–609.
    1. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR. Mechanisms of cancer‐related fatigue. Oncologist 2007;12:22–34.
    1. David MP, Walsh D. Mechanisms of fatigue. J Support Oncol 2010;8:164–174.
    1. Shafqat A, Einhorn LH, Hanna N, Sledge GW, Hanna A, Juliar BE, et al. Screening studies for fatigue and laboratory correlates in cancer patients undergoing treatment. Ann Oncol 2005;16:1545–1550.
    1. al‐Majid S, Do MC. Cancer‐induced fatigue and skeletal muscle wasting: the role of exercise. Biol Res Nurs 2001;2:186–197.
    1. Cantarero‐Villanueva I, Fernandez‐Lao C, Cuesta‐Vargas AI, Del Moral‐Avila R, Fernandez‐de‐Las‐Penas C, Arroyo‐Morales M. The effectiveness of a deep water aquatic exercise program in cancer‐related fatigue in breast cancer survivors: a randomized controlled trial. Arch Phys Med Rehabil 2013;94:221–230.
    1. Strasser B, Steindorf K, Wiskemann J, Ulrich CM. Impact of resistance training in cancer survivors: a meta‐analysis. Med Sci Sports Exerc 2013;45:2080–2090.
    1. Kampshoff CS, Chinapaw MJ, Brug J, Twisk JW, Schep G, Nijziel MR, et al. Randomized controlled trial of the effects of high intensity and low‐to‐moderate intensity exercise on physical fitness and fatigue in cancer survivors: results of the Resistance and Endurance exercise After ChemoTherapy (REACT) study. BMC Med 2015;13:275.
    1. van Waart H, Stuiver MM, van Harten WH, Geleijn E, Kieffer JM, Buffart LM, et al. Effect of low‐intensity physical activity and moderate‐ to high‐intensity physical exercise during adjuvant chemotherapy on physical fitness, fatigue, and chemotherapy completion rates: results of the PACES randomized clinical trial. J Clin Oncol 2015;33:1918–1927.
    1. Mustian KM, Peppone L, Darling TV, Palesh O, Heckler CR, Morrow GR. A 4‐week home‐based aerobic and resistance exercise program during radiation therapy: a pilot randomized clinical trial. J Support Oncol 2009;7:158–167.
    1. Hansen PA, Dechet CB, Porucznik CA, LaStayo PC. Comparing eccentric resistance exercise in prostate cancer survivors on and off hormone therapy: a pilot study. PMR 2009;1:1019–1024.
    1. Galvao DA, Taaffe DR, Spry N, Joseph D, Newton RU. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol 2010;28:340–347.
    1. Hanson ED, Sheaff AK, Sood S, Ma L, Francis JD, Goldberg AP, et al. Strength training induces muscle hypertrophy and functional gains in black prostate cancer patients despite androgen deprivation therapy. J Gerontol A Biol Sci Med Sci 2013;68:490–498.
    1. Cormie P, Newton RU, Spry N, Joseph D, Taaffe DR, Galvao DA. Safety and efficacy of resistance exercise in prostate cancer patients with bone metastases. Prostate Cancer Prostatic Dis 2013;16:328–335.
    1. Jones LW, Friedman AH, West MJ, Mabe SK, Fraser J, Kraus WE, et al. Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma. Cancer 2010;116:695–704.
    1. Kilgour RD, Vigano A, Trutschnigg B, Hornby L, Lucar E, Bacon SL, et al. Cancer‐related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer. J Cachexia Sarcopenia Muscle 2010;1:177–185.
    1. Blauwhoff‐Buskermolen S, de van der Schueren MA, Verheul HM, Langius JA. ‘Pre‐cachexia’: a non‐existing phenomenon in cancer? Ann Oncol 2014;25:1668–1669.
    1. Blauwhoff‐Buskermolen S, Versteeg KS, de van der Schueren MA, den Braver NR, Berkhof J, Langius JA, et al. Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer. J Clin Oncol 2016;34:1339–1344.
    1. Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other anemia‐related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manage 1997;13:63–74.
    1. Dittner AJ, Wessely SC, Brown RG. The assessment of fatigue: a practical guide for clinicians and researchers. J Psychosom Res 2004;56:157–170.
    1. Barsevick AM, Cleeland CS, Manning DC, O'Mara AM, Reeve BB, Scott JA, et al. ASCPRO recommendations for the assessment of fatigue as an outcome in clinical trials. J Pain Symptom Manage 2010;39:1086–1099.
    1. Manir KS, Bhadra K, Kumar G, Manna A, Patra NB, Sarkar SK. Fatigue in breast cancer patients on adjuvant treatment: course and prevalence. Indian J Palliat Care 2012;18:109–116.
    1. Van Belle S, Paridaens R, Evers G, Kerger J, Bron D, Foubert J, et al. Comparison of proposed diagnostic criteria with FACT‐F and VAS for cancer‐related fatigue: proposal for use as a screening tool. Support Care Cancer 2005;13:246–254.
    1. Shen W, Punyanitya M, Wang Z, Gallagher D, St‐Onge MP, Albu J, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross‐sectional image. J Appl Physiol(1985) 2004;97:2333–2338.
    1. Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab 2008;33:997–1006.
    1. Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol (1985) 1998;85:115–122.
    1. Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McGargar LJ, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 2013;31:1539–1547.
    1. Jones LW, Friedman AH, West MJ, Mabe SK, Fraser J, Kraus WE, et al. Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma. Cancer 2010;116:695–704.
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–383.
    1. Prado CM, Birdsell LA, Baracos VE. The emerging role of computerized tomography in assessing cancer cachexia. Curr Opin Support Palliat Care 2009;3:269–275.
    1. MacDonald AJ, Greig CA, Baracos V. The advantages and limitations of cross‐sectional body composition analysis. Curr Opin Support Palliat Care 2011;5:342–349.
    1. Lövgren M, Tishelman C, Sprangers M, Koyi H, Hamberg K. Symptoms and problems with functioning among women and men with inoperable lung cancer—a longitudinal study. Lung Cancer 2008;60:113–124.
    1. von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015. J Cachexia Sarcopenia Muscle 2015;6:315–316.

Source: PubMed

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