Principal Investigator

Elizabeth Marjorie Cespedes
Feliciano
Awardee Organization

Kaiser Foundation Research Institute
United States

Fiscal Year
2023
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

D3-creatine dilution to determine skeletal muscle mass in colon cancer patients

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the United States. Using clinicallyacquired computed tomography (CT) scans to measure muscle cross-sectional area (CSA), the prevalence of low muscle in nonmetastatic CRC patients is estimated to be 42%. Low CT CSA has been associated with a more than 2-fold increased risk of chemotoxicity, a 26% increased risk of surgical complication and a 46% increased risk of CRC-specific death. However, the use of CT to estimate muscle mass is constrained because CT is not the standard of care in all cancers, is often limited to one anatomic region and cannot distinguish between contractile muscle protein and other tissue in muscle fascia. Alternatives include dual energy x-ray absorptiometry (DXA), which measures all lean body mass (LBM), including fibrotic and connective tissue, water, and organs. However, neither DXA nor CT directly quantifies total body muscle mass and both methods expose patients to radiation. Safe and non-invasive methods to assess muscle mass will contribute to our understanding of the mechanisms by which muscle loss may affect morbidity and mortality after cancer and enhance interventions such as physical activity that target muscle mass in cancer patients. To this end, for the first time in cancer patients, the proposed study will evaluate the associations of a direct and non-invasive method to assess total body muscle mass with outcomes. Deuterated creatine dilution (d3-creatine) estimates total creatine pool size, and thus muscle mass, using an oral dose of d3-creatine and measuring d3-creatinine enrichment in a single, spot-urine sample a few days later. Since creatine is located within the contractile components of the sarcomere, d3-creatine dilution provides a measure of functional muscle mass. This study will measure d3-creatine muscle mass in 90 colon cancer patients participating in a randomized controlled trial of resistance training during chemotherapy in which CT CSA and DXA LBM are already being collected. We will test whether d3-creatine muscle mass changes in response to resistance training and examine whether d3creatine muscle mass is associated functional, metabolic, inflammatory and chemotherapy outcomes. In addition, we will compare the strength of the associations with outcomes found with d3-creatine muscle mass to those with CT CSA and/or DXA LBM. If d3-creatine muscle mass in cancer patients is predictive of strength, function, chemotoxicity and cancer-related biomarkers, then d3-creatine dilution will be a useful tool for research on the role of muscle mass and physical activity interventions in cancer patients. In the future, informed by the evidence generated in this study, the simple d3-creatine dilution test might someday be used clinically to identify cancer patients with low muscle mass for interventions to mitigate chemotoxicity, cardiometabolic risk, functional impairment and mortality.

Publications

  • Caan BJ, Brown JC, Lee C, Binder AM, Weltzien E, Ross MC, Quesenberry CP, Campbell KL, Cespedes Feliciano EM, Castillo A, Quinney S, Yang S, Meyerhardt JA, Schmitz KH. Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial. Cancer. 2024 Jan 24. Epub 2024 Jan 24. PMID: 38265970
  • Cespedes Feliciano EM, Hohensee C, Rosko AE, Anderson GL, Paskett ED, Zaslavsky O, Wallace RB, Caan BJ. Association of Prediagnostic Frailty, Change in Frailty Status, and Mortality After Cancer Diagnosis in the Women's Health Initiative. JAMA network open. 2020 Sep 1;3(9):e2016747. PMID: 32926116
  • Caan BJ, Meyerhardt JA, Brown JC, Campbell KL, Cespedes Feliciano EM, Lee C, Ross MC, Quinney S, Quesenberry C, Sternfeld B, Schmitz KH. Recruitment strategies and design considerations in a trial of resistance training to prevent dose-limiting toxicities in colon cancer patients undergoing chemotherapy. Contemporary clinical trials. 2021 Feb;101:106242. Epub 2020 Dec 7. PMID: 33301991
  • Cheng E, Kirley J, Cespedes Feliciano EM, Caan BJ. Adiposity and cancer survival: a systematic review and meta-analysis. Cancer causes & control : CCC. 2022 Oct;33(10):1219-1246. Epub 2022 Aug 15. PMID: 35971021
  • Cheng E, Caan BJ, Cawthon PM, Evans WJ, Hellerstein MK, Shankaran M, Campbell KL, Binder AM, Sternfeld B, Meyerhardt JA, Schmitz KH, Cespedes Feliciano EM. D3-creatine dilution, computed tomography and dual-energy X-ray absorptiometry for assessing myopenia and physical function in colon cancer: A cross-sectional study. Journal of cachexia, sarcopenia and muscle. 2023 Dec;14(6):2768-2778. Epub 2023 Oct 30. PMID: 37899757
  • Brown JC, Caan BJ, Cespedes Feliciano EM, Xiao J, Weltzien E, Prado CM, Kroenke CH, Castillo A, Kwan ML, Meyerhardt JA. Weight stability masks changes in body composition in colorectal cancer: a retrospective cohort study. The American journal of clinical nutrition. 2021 Jun 1;113(6):1482-1489. PMID: 33668052
  • Cheng E, Caan BJ, Cawthon PM, Evans WJ, Hellerstein MK, Shankaran M, Nyangau E, Campbell KL, Lee C, Binder AM, Meyerhardt JA, Schmitz KH, Cespedes Feliciano EM. Body Composition, Relative Dose Intensity, and Adverse Events among Patients with Colon Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2023 Oct 2;32(10):1373-1381. PMID: 37450841
  • Feliciano EMC, Winkels RM, Meyerhardt JA, Prado CM, Afman LA, Caan BJ. Abdominal adipose tissue radiodensity is associated with survival after colorectal cancer. The American journal of clinical nutrition. 2021 Dec 1;114(6):1917-1924. PMID: 34510172
  • Pichardo MS, Esserman D, Ferrucci LM, Molina Y, Chlebowski RT, Pan K, Garcia DO, Lane DS, Shadyab AH, Lopez-Pentecost M, Luo J, Kato I, Springfield S, Rosal MC, Bea JW, Cespedes Feliciano EM, Qi L, Nassir R, Snetselaar L, Manson J, Bird C, Irwin ML. Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity-related cancer risk and mortality in Black and Latina Women's Health Initiative participants. Cancer. 2022 Oct;128(20):3630-3640. Epub 2022 Aug 23. PMID: 35996861
  • Luo J, Carter SJ, Feliciano EMC, Hendryx M. Trajectories of objectively measured physical function among older breast cancer survivors in comparison with cancer-free controls. Breast cancer research and treatment. 2022 Jun;193(2):467-476. Epub 2022 Mar 26. PMID: 35347550