Lean body mass, muscle fibre size and muscle function in cancer patients during chemotherapy and 10 weeks exercise.

Simon Lønbro, Jean Farup, Signe Bentsen, Thomas Voss, Nikolaj Rittig, Jakob Wang, Morten Ørskov, Inger Højris, Ulla Ramer Mikkelsen


Background: Chemotherapy can reduce muscle mass in cancer patients but the potential of exercise to ameliorate this are understudied, particularly at the myocellular level. The primary purpose was to investigate changes in lean body mass (LBM) and secondly single fibre cross-sectional area (CSA) in cancer patients during chemotherapy and in combination with 10 weeks of exercise. Methods: In a single-arm trial, patients adhered to chemotherapy for at least 4 weeks (control period) before 10 weeks of exercise adjunct to chemotherapy (exercise period). LBM (Dual Energy X-ray Absorptiometry) and single fibre CSA (muscle biopsies) were assessed at baseline, pre- and post-exercise.  Muscle strength, functional performance and aerobic capacity were also assessed. Results: Ten patients were included, however only six patients completed the protocol. LBM changed over time (p=0.013), but no significant changes were observed between specific time points. Numerically, LBM decreased by 0.3 kg (p=0.41, 95% CI: -1.1;0.5) from 41.3-41.0 kg, during the control period and increased by 0.7 kg (p=0.16, 95% CI: -0.6;2.0) from 40.4-41.1 kg during exercise. Muscle fibre CSA did not change significantly over time (p=0.13), but decreased numerically in the control period by 703 μm2 (p=0.20, 95% CI: -1877; 470) and increased by 846 μm2 (trend, p=0.08, 95% CI: -162; 1854) following exercise. Muscle strength and functional performance were unchanged during the control period but improved post-exercise. Conclusions:  Despite non-significant changes in muscle mass (due to small sample size), this study adds novel information on LBM and myocellular changes in cancer patients during chemotherapy and concurrent exercise.

Full Text:




Adamsen, L., Quist M Fau - Andersen, C., Andersen C Fau - Moller, T., Moller T Fau - Herrstedt, J., Herrstedt J Fau - Kronborg, D., Kronborg D Fau - Baadsgaard, M. T., et al. (2009). Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ 339, b3410. doi:D - NLM: PMC2762035 EDAT- 2009/10/15 06:00 MHDA- 2009/10/30 06:00 CRDT- 2009/10/15 06:00 PST - epublish.

Adamsen, L., Quist, M., Midtgaard, J., Andersen, C., Moller, T., Knutsen, L., et al. (2006). The effect of a multidimensional exercise intervention on physical capacity, well-being and quality of life in cancer patients undergoing chemotherapy. Support Care Cancer 14, 116–127. doi:10.1007/s00520-005-0864-x.

Andersen, J. L. (2003). Muscle fibre type adaptation in the elderly human muscle. Scand. J. Med. Sci. Sports 13, 40–47. doi:0299 [pii].

Antoun, S., Birdsell, L., Sawyer, M. B., Venner, P., Escudier, B., and Baracos, V. E. (2010). Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J Clin Oncol 28, 1054–1060. doi:10.1200/jco.2009.24.9730.

Apro, W., Wang, L., Ponten, M., Blomstrand, E., and Sahlin, K. (2013). Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle. Am J Physiol Endocrinol Metab 305, E22–32. doi:10.1152/ajpendo.00091.2013.

Bergstrom, J. (1975). Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest 35, 609–616.

Blauwhoff-Buskermolen, S., Versteeg, K. S., de van der Schueren, M. A., den Braver, N. R., Berkhof, J., Langius, J. A., et al. (2016). Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. J Clin Oncol. doi:10.1200/jco.2015.63.6043.

Bonifati, D. M., Ori, C., Rossi, C. R., Caira, S., Fanin, M., and Angelini, C. (2000). Neuromuscular damage after hyperthermic isolated limb perfusion in patients with melanoma or sarcoma treated with chemotherapeutic agents. Cancer Chemother Pharmacol 46, 517–522. doi:10.1007/s002800000175.

Christensen, J. F., Jones, L. W., Andersen, J. L., Daugaard, G., Rorth, M., and Hojman, P. (2014a). Muscle dysfunction in cancer patients. Ann Oncol. doi:10.1093/annonc/mdt551.

Christensen, J. F., Jones, L. W., Tolver, A., Jorgensen, L. W., Andersen, J. L., Adamsen, L., et al. (2014b). Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: a randomized controlled trial. Br J Cancer 111, 8–16. doi:10.1038/bjc.2014.273.

Courneya, K. S., Segal, R. J., Mackey, J. R., Gelmon, K., Reid, R. D., Friedenreich, C. M., et al. (2007). Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol 25, 4396–4404. doi:10.1200/jco.2006.08.2024.

Dalgas, U., Stenager, E., Jakobsen, J., Petersen, T., Hansen, H. J., Knudsen, C., et al. (2009). Resistance training improves muscle strength and functional capacity in multiple sclerosis. Neurology 73, 1478–1484. doi:10.1212/WNL.0b013e3181bf98b4.

Ellegard, L. H., Ahlen, M., Korner, U., Lundholm, K. G., Plank, L. D., and Bosaeus, I. G. (2009). Bioelectric impedance spectroscopy underestimates fat-free mass compared to dual energy X-ray absorptiometry in incurable cancer patients. Eur J Clin Nutr 63, 794–801. doi:10.1038/ejcn.2008.35.

Fry, A. C. (2004). The role of resistance exercise intensity on muscle fibre adaptations. Sport. Med 34, 663–679. PubMed PMID: 15335243.

Fyfe, J. J., Bishop, D. J., and Stepto, N. K. (2014). Interference between concurrent resistance and endurance exercise: molecular bases and the role of individual training variables. Sport. Med 44, 743–762. doi:10.1007/s40279-014-0162-1.

Galvao, D. A., Nosaka, K., Taaffe, D. R., Spry, N., Kristjanson, L. J., McGuigan, M. R., et al. (2006). Resistance training and reduction of treatment side effects in prostate cancer patients. Med.Sci.Sports Exerc. 38, 2045–2052. doi:10.1249/01.mss.0000233803.48691.8b.

Galvao, D. A., Taaffe, D. R., Spry, N., Joseph, D., and Newton, R. U. (2010). 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 28, 340–347. doi:10.1200/jco.2009.23.2488.

Hvid, L., Aagaard, P., Justesen, L., Bayer, M. L., Andersen, J. L., Ortenblad, N., et al. (2010). Effects of aging on muscle mechanical function and muscle fiber morphology during short-term immobilization and subsequent retraining. J Appl Physiol 109, 1628–1634. doi:10.1152/japplphysiol.00637.2010.

Johns, N., Hatakeyama, S., Stephens, N. A., Degen, M., Degen, S., Frieauff, W., et al. (2014). Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle. PLoS One 9, e83618. doi:10.1371/journal.pone.0083618.

Johns, N., Stephens, N. A., and Fearon, K. C. (2013). Muscle wasting in cancer. Int J Biochem Cell Biol 45, 2215–2229. doi:10.1016/j.biocel.2013.05.032.

Kang, S. H., Cho, K. H., Park, J. W., Yoon, K. W., and Do, J. Y. (2013). Comparison of bioimpedance analysis and dual-energy X-ray absorptiometry body composition measurements in peritoneal dialysis patients according to edema. Clin Nephrol 79, 261–268. doi:10.5414/cn107693.

Kouroussis, C., Xydakis, E., Potamianou, A., Giannakakis, T., Kakolyris, S., Agelaki, S., et al. (1999). Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: a multicenter dose-escalation study. The Greek Breast Cancer Cooperative Group (GBCCG). Ann Oncol 10, 547–552. Available at: http://annonc.oxfordjournals.org/content/10/5/547.full.pdf.

Kraemer, W. J., Ratamess, N. A., and French, D. N. (2002). Resistance training for health and performance. Curr.Sports Med.Rep. 1, 165–171.

Leenders, M., Verdijk, L. B., van der Hoeven, L., van Kranenburg, J., Nilwik, R., and van Loon, L. J. (2013). Elderly men and women benefit equally from prolonged resistance-type exercise training. J Gerontol A Biol Sci Med Sci 68, 769–779. doi:10.1093/gerona/gls241.

Lexell, J. (1993). Ageing and human muscle: observations from Sweden. Can J Appl Physiol 18, 2–18. Available at: http://www.nrcresearchpress.com/doi/abs/10.1139/h93-002.

Lexell, J., Taylor, C. C., and Sjostrom, M. (1988). What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci 84, 275–294.

Lønbro, S. (2014). The effect of progressive resistance training on lean body mass in post-treatment cancer patients - A systematic review. Radiother Oncol 110, 71–80. doi:10.1016/j.radonc.2013.07.008.

Lønbro, S., Dalgas, U., Primdahl, H., Johansen, J., Nielsen, J. L., Aagaard, P., et al. (2013a). Progressive resistance training rebuilds lean body mass in head and neck cancer patients after radiotherapy - Results from the randomized DAHANCA 25B trial. Radiother Oncol. doi:10.1016/j.radonc.2013.07.002.

Lønbro, S., Dalgas, U., Primdahl, H., Johansen, J., Nielsen, J. L., Overgaard, J., et al. (2013b). Lean body mass and muscle function in head and neck cancer patients and healthy individuals--results from the DAHANCA 25 study. Acta Oncol 52, 1543–51. doi:10.3109/0284186x.2013.822553.

Lønbro, S., Dalgas, U., Primdahl, H., Overgaard, J., Overgaard, K., Lønbro, S., et al. (2013c). Feasibility and efficacy of progressive resistance training and dietary supplements in radiotherapy treated head and neck cancer patients-the DAHANCA 25A study. Acta Oncol. (Madr). 52, 310–318. doi:10.3109/0284186x.2012.741325.

Massicotte, M. H., Borget, I., Broutin, S., Baracos, V. E., Leboulleux, S., Baudin, E., et al. (2013). Body composition variation and impact of low skeletal muscle mass in patients with advanced medullary thyroid carcinoma treated with vandetanib: results from a placebo-controlled study. J Clin Endocrinol Metab 98, 2401–2408. doi:10.1210/jc.2013-1115.

Nilsen, T. S., Raastad, T., Skovlund, E., Courneya, K. S., Langberg, C. W., Lilleby, W., et al. (2015a). Effects of strength training on body composition, physical functioning, and quality of life in prostate cancer patients during androgen deprivation therapy. Acta Oncol, 1–9. doi:10.3109/0284186x.2015.1037008.

Nilsen, T. S., Thorsen, L., Fossa, S. D., Wiig, M., Kirkegaard, C., Skovlund, E., et al. (2015b). Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy. Scand J Med Sci Sport. doi:10.1111/sms.12543.

Pedersen, B. K., and Febbraio, M. A. (2012). Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8, 457–465. doi:10.1038/nrendo.2012.49.

Pedersen, L., Idorn, M., Olofsson, G. H., Lauenborg, B., Nookaew, I., Hansen, R. H., et al. (2016). Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. Cell Metab. doi:10.1016/j.cmet.2016.01.011.

Peterson, M. D., Sen, A., and Gordon, P. M. (2011). Influence of resistance exercise on lean body mass in aging adults: a meta-analysis. Med Sci Sport. Exerc 43, 249–258. doi:10.1249/MSS.0b013e3181eb6265.

Prado, C. M., Baracos, V. E., McCargar, L. J., Reiman, T., Mourtzakis, M., Tonkin, K., et al. (2009). Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 15, 2920–2926. doi:10.1158/1078-0432.ccr-08-2242.

Prado, C. M., Lieffers, J. R., McCargar, L. J., Reiman, T., Sawyer, M. B., Martin, L., et al. (2008). Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9, 629–635. doi:10.1016/s1470-2045(08)70153-0.

Ratamess, N. A. (2009). American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med.Sci.Sports Exerc. 41, 687–708. doi:10.1249/MSS.0b013e3181915670.

Reid, K. F., and Fielding, R. A. (2012). Skeletal muscle power: a critical determinant of physical functioning in older adults. Exerc Sport Sci Rev 40, 4–12. doi:10.1097/JES.0b013e31823b5f13.

Ross, P. J., Ashley, S., Norton, A., Priest, K., Waters, J. S., Eisen, T., et al. (2004). Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? Br J Cancer 90, 1905–1911. doi:10.1038/sj.bjc.6601781.

Semb, K. A., Aamdal, S., and Oian, P. (1998). Capillary protein leak syndrome appears to explain fluid retention in cancer patients who receive docetaxel treatment. J. Clin. Oncol. 16, 3426–3432.

Sorensen, J. B., Kragstrup, J., Kjaer, K., and Puggaard, L. (2007). Exercise on prescription: trial protocol and evaluation of outcomes. BMC Heal. Serv Res 7, 36. doi:10.1186/1472-6963-7-36.

Suetta, C., Andersen, J. L., Dalgas, U., Berget, J., Koskinen, S., Aagaard, P., et al. (2008). Resistance training induces qualitative changes in muscle morphology, muscle architecture, and muscle function in elderly postoperative patients. J Appl Physiol 105, 180–186. doi:01354.2007 [pii]10.1152/japplphysiol.01354.2007 [doi].

Tarnopolsky, M. A., Pearce, E., Smith, K., and Lach, B. (2011). Suction-modified Bergstrom muscle biopsy technique: experience with 13,500 procedures. Muscle Nerve 43, 717–725. doi:10.1002/mus.21945.

Tsai, S. (2012). Importance of lean body mass in the oncologic patient. Nutr Clin Pr. 27, 593–598. doi:10.1177/0884533612457949.

Visovsky, C. (2006). Muscle strength, body composition, and physical activity in women receiving chemotherapy for breast cancer. Integr Cancer Ther 5, 183–191. doi:10.1177/1534735406291962.

Yip, C., Goh, V., Davies, A., Gossage, J., Mitchell-Hay, R., Hynes, O., et al. (2014). Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer. Eur Radiol 24, 998–1005. doi:10.1007/s00330-014-3110-4.

DOI: http://dx.doi.org/10.17987/jcsm-cr.v2i1.26


  • There are currently no refbacks.