Body composition skeletal muscle analysis in cancer cachexia studies: Is there a place for 3T MRI analysis?

Elaine Sandra Rogers, William Ormiston, Rachel Heron, Beau Pontré, Roderick MacLeod, Anthony Doyle

Abstract


Background: Cancer cachexia is a condition often seen in end stage Non-Small Cell Lung Cancer (NSCLC) patients. Recent developments include the use of pharmaceutical agents and/or exercise to induce stability/hypertrophy of muscle volume. This requires accurate assessment of the change in both quantity and quality of the muscle during cancer cachexia clinical studies. 3T Magnetic Resonance Imaging (MRI) is appropriately placed to address both of these factors. 

Methods: Auckland’s Cancer Cachexia evaluating Resistance Training (ACCeRT) study is a randomised controlled feasibility study investigating eicosapentaenoic acid (EPA) and cyclo-oxygenase-2 (COX-2) inhibitor (celebrex) (Arm A) versus EPA, COX-2 inhibitor (celebrex), Progressive Resistance Training (PRT) plus essential amino acids (EAAs) high in leucine (Arm B) in NSCLC cachectic patients. All participants underwent 3T MRI scanning at baseline and at last or end of trial (EOT) visit.

Results: Analysis showed a mean total quadriceps muscle volume percentage change from baseline to EOT of +12.47% (Arm A), compared with -2.96% (Arm B). There was a difference in muscle volume between genders. Arm B participant data showed a percentage change of +4.23% within females (n=2) compared with ˗10.15% (n=2) within males at EOT visit. All EOT results suggests the use of EPA and celecoxib +/- PRT and EAAs could potentially preserve muscle volume loss during refractory cachexia.

Conclusion: ACCeRT is the first study to utilise 3T MRI total quadriceps muscle volume within a cancer cachexia study, along with the first in an end-stage/refractory cachexia population. These results can be used for baseline/reference for future cancer cachexia studies targeting the anabolic muscle pathways in end˗stage/refractory cachexia patients.


Full Text:

PDF

References


Fearon KCH, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. The Lancet Oncology. 2011;12:489-95.

Muscaritoli M, Bossola M, Aversa Z, Bellantone R, Rossi-Fanelli F. Prevention and treatment of cancer cachexia: New insights into an old problem. European Journal of Cancer. 2006;42:31-41.

Di Sebastiano KM, Mourtzakis M. A critical evaluation of body composition modalities used to assess adipose and skeletal muscle tissue in cancer. Applied Physiology, Nutrition, and Metabolism. 2012;37:811-21.

Trutschnigg B, Kilgour RD, Reinglas J, Rosenthall L, Hornby L, Morais JA, et al. Precision and reliability of strength (Jamar vs. Biodex handgrip) and body composition (dual-energy X-ray absorptiometry vs. bioimpedance analysis) measurements in advanced cancer patients. Applied Physiology, Nutrition, and Metabolism. 2008;33:1232-9.

Thomson R, Brinkworth GD, Buckley JD, Noakes M, Clifton PM. Good agreement between bioelectrical impedance and dual-energy X-ray absorptiometry for estimating changes in body composition during weight loss in overweight young women. Clinical Nutrition. 2007;26:771-7.

Yip C, Dinkel C, Mahajan A, Siddique M, Cook GJR, Goh V. Imaging body composition in cancer patients: visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome. Insights into Imaging. 2015;6:489-97.

Boutin RD, Yao L, Canter RJ, Lenchik L. Sarcopenia: Current Concepts and Imaging Implications. American Journal of Roentgenology. 2015;205:W255-W66.

Madeddu C, Macciò A, Astara G, Massa E, Dessì M, Antoni G, et al. Open phase II study on efficacy and safety of an oral amino acid functional cluster supplementation in cancer cachexia. Mediterranean Journal of Nutrition and Metabolism. 2010;3:165-72.

Del Fabbro E, Dev R, Hui D, Palmer L, Bruera E. Effects of Melatonin on Appetite and Other Symptoms in Patients With Advanced Cancer and Cachexia: A Double-Blind Placebo-Controlled Trial. Journal of Clinical Oncology. 2013;31:1271-6.

Bayliss TJ, Smith JT, Schuster M, Dragnev KH, Rigas JR. A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer. Expert Opinion on Biological Therapy. 2011;11:1663-8.

Macciò A, Madeddu C, Gramignano G, Mulas C, Floris C, Sanna E, et al. A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: Evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecologic Oncology. 2012;124:417-25.

Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. The Lancet Oncology. 2013;14:335-45.

Temel JS, Abernethy AP, Currow DC, Friend J, Duus EM, Yan Y, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. The Lancet Oncology. 2016;17:519-31.

Stewart Coats AJ, Ho GF, Prabhash K, von Haehling S, Tilson J, Brown R, et al. Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non‐small cell lung cancer or colorectal cancer: a randomized, double‐blind, placebo‐controlled, international multicentre phase II study (the ACT‐ONE trial). Journal of Cachexia, Sarcopenia and Muscle. 2016;7:355-65.

Mantovani G, Macciò A, Madeddu C, Serpe R, Massa E, Dessì M, et al. Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia. The Oncologist. 2010;15:200-11.

Madeddu C, Dessì M, Panzone F, Serpe R, Antoni G, Cau MC, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clinical Nutrition. 2012;31:176-82.

Scott JM, Martin DS, Ploutz-Snyder R, Matz T, Caine T, Downs M, et al. Panoramic ultrasound: a novel and valid tool for monitoring change in muscle mass. Journal of Cachexia, Sarcopenia and Muscle. 2017;8:475-81.

Mourtzakis M, Prado CMM, 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. Applied Physiology, Nutrition, and Metabolism. 2008;33:997-1006.

Morse CI, Degens H, Jones DA. The validity of estimating quadriceps volume from single MRI cross-sections in young men. European Journal of Applied Physiology. 2007;100:267-74.

Hudelmaier M, Wirth W, Himmer M, Ring-Dimitriou S, Sänger A, Eckstein F. Effect of exercise intervention on thigh muscle volume and anatomical cross-sectional areas—Quantitative assessment using MRI. Magnetic Resonance in Medicine. 2010;64:1713-20.

Weber M-A, Krakowski-Roosen H, Schröder L, Kinscherf R, Krix M, Kopp-Schneider A, et al. Morphology, metabolism, microcirculation, and strength of skeletal muscles in cancer-related cachexia. Acta Oncologica. 2009;48:116-24.

Gray C, MacGillivray TJ, Eeley C, Stephens NA, Beggs I, Fearon KC, et al. Magnetic resonance imaging with k-means clustering objectively measures whole muscle volume compartments in sarcopenia/cancer cachexia. Clinical Nutrition. 2011;30:106-11.

Rogers ES, MacLeod RD, Stewart J, Bird SP, Keogh JWL. A randomised feasibility study of EPA and Cox-2 inhibitor (Celebrex) versus EPA, Cox-2 inhibitor (Celebrex), Resistance Training followed by ingestion of essential amino acids high in leucine in NSCLC cachectic patients - ACCeRT Study. BMC Cancer. 2011;11:493.

Yushkevich PA, Piven J, Hazlett HC, Smith RG, Ho S, Gee JC, et al. User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability. NeuroImage. 2006;31:1116-28.

Chao P. 3T MRI is better: Size does matter. The Internet Journal of Radiology. 2007;9:1-4.

Wong S, Steinbach L, Zhao J, Stehling C, Ma CB, Link TM. Comparative study of imaging at 3.0 T versus 1.5 T of the knee. Skeletal Radiology. 2009;38:761-9.

Chu R, Tauhid S, Glanz BI, Healy BC, Kim G, Oommen VV, et al. Whole Brain Volume Measured from 1.5T versus 3T MRI in Healthy Subjects and Patients with Multiple Sclerosis. Journal of Neuroimaging. 2016;26:62-7.

Greig CA, Johns N, Gray C, MacDonald A, Stephens NA, Skipworth RJE, et al. Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Support Care Cancer. 2014;22:1269-75.

Baudin P-Y, Azzabou N, Carlier PG. Fast and user-friendly interactive segmentation of skeletal muscles in nuclear magnetic resonance images will facilitate quantitation of sarcopenia. Journal of Cachexia, Sarcopenia and Muscle 2015;6(Abstract 1-18):398-509.

Le-Rademacher JG, Crawford J, Evans WJ, Jatoi A. Overcoming obstacles in the design of cancer anorexia/weight loss trials. Critical Reviews in Oncology / Hematology. 2017;117:30-7.

Clinicaltrials.gov. Brown Adipose Tissue Activity and Energy Metabolism in Cachexia (BAT-Cachexia) 2015. https://clinicaltrials.gov/ct2/show/NCT02500004. Accessed 10 November 2017.

Fragala MS, Kenny AM, Kuchel GA. Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment. Sports Medicine. 2015;45:641-58.

Calvani R, Marini F, Cesari M, Buford TW, Manini TM, Pahor M, et al. Systemic inflammation, body composition, and physical performance in old community-dwellers. Journal of Cachexia, Sarcopenia and Muscle. 2017;8:69-77.

von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015. Journal of Cachexia, Sarcopenia and Muscle. 2015;6:315-6.




DOI: http://dx.doi.org/10.17987/jcsm-cr.v3i2.59

Refbacks

  • There are currently no refbacks.