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

D3-肌酸稀释液测定结肠癌患者的骨骼肌质量

• 批准号: 10337029
• 负责人: Elizabeth Marjorie Cespedes Feliciano
• 金额: $ 37.92万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10337029
• 关键词: Abdomen; Affect; Aging; Anatomy; Area; Biological Markers; Blood Pressure; Cancer Patient; Carcinoembryonic Antigen; Cessation of life; Clinical; Colon Carcinoma; Colorectal Cancer; Connective Tissue; Creatine; Creatinine; Data; Dose; Dose-Limiting; Dual-Energy X-Ray Absorptiometry; Enrollment; Fascia; Fasting; Funding; Future; Glucose; Hand Strength; Inflammation; Inflammatory; Intervention; Lead; Lipids; Low Prevalence; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Metabolic; Methods; Monitor; Morbidity - disease rate; Muscle; Muscle Proteins; Muscular Atrophy; Nonmetastatic; Oncology; Oral; Organ; Outcome; Patients; Performance Status; Physical Function; Physical Performance; Physical activity; Proxy; Radiation; Randomized; Randomized Controlled Trials; Recurrent disease; Research; Risk; Risk Factors; Role; Sampling; Sarcomeres; Scanning; Site; Skeletal Muscle; Skin; Spottings; Surgical complication; Testing; Thinness; Time; Tissues; Toxic effect; Toxicity due to chemotherapy; Treatment Side Effects; United States; Urine; Validation; Waiting Lists; Water; X-Ray Computed Tomography; cancer diagnosis; cancer risk; cancer survival; cardiometabolic risk; chemotherapy; cohort; colon cancer patients; colorectal cancer risk; comparison intervention; cost effective; design; disability; exercise intervention; fall injury; functional disability; functional status; intervention effect; lean body mass; mortality; muscle form; older men; reduced muscle mass; resistance exercise; response; standard of care; strength training; surgical risk; tool; treatment risk

ABSTRACT Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the United States. Using clinically- acquired 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 d3- creatine 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.

抽象的 结直肠癌 (CRC) 是美国第四大最常诊断的癌症。临床上使用—— 获得计算机断层扫描（CT）扫描来测量肌肉横截面积（CSA）， 非转移性 CRC 患者的肌肉水平低下估计为 42%。低 CT CSA 与 化学毒性风险增加超过 2 倍，手术并发症风险增加 26%，手术并发症风险增加 46% CRC 特异性死亡风险增加。然而，使用 CT 来估计肌肉质量受到限制，因为 CT 并非所有癌症的治疗标准，通常仅限于某一解剖区域且无法区分 收缩性肌肉蛋白和肌肉筋膜中的其他组织之间。替代方案包括双能 X 射线 吸收测定法（DXA），测量所有去脂体重（LBM），包括纤维化组织和结缔组织， 水、器官。然而，DXA 和 CT 都不能直接量化全身肌肉质量，并且这两种方法 让患者受到辐射。评估肌肉质量的安全和非侵入性方法将有助于我们 了解肌肉损失可能影响癌症和癌症后发病率和死亡率的机制 加强干预措施，例如针对癌症患者肌肉质量的体育活动。为此，为了 拟议的研究将首次在癌症患者中评估直接和非侵入性的关联 评估全身肌肉质量和结果的方法。氘代肌酸稀释度（d3-肌酸）估计值 使用口服剂量的 d3-肌酸并测量 d3-肌酐，得出总肌酸池大小，从而得出肌肉质量 几天后在单一的点尿样本中富集。由于肌酸位于收缩肌内 肌节的成分，d3-肌酸稀释液提供了功能性肌肉质量的测量。这项研究 将测量参加随机对照试验的 90 名结肠癌患者的 d3-肌酸肌肉质量 化疗期间的阻力训练，其中 CT CSA 和 DXA LBM 已被收集。我们 将测试 d3-肌酸肌肉质量是否因阻力训练而变化，并检查 d3- 肌酸肌肉质量与功能、代谢、炎症和化疗结果相关。在 此外，我们将比较关联强度与 d3-肌酸肌肉质量的结果 患有 CT CSA 和/或 DXA LBM 的患者。如果癌症患者的 d3-肌酸肌肉质量可以预测力量， 功能、化学毒性和癌症相关生物标志物，那么 d3-肌酸稀释液将是一个有用的工具 研究肌肉质量和身体活动干预对癌症患者的作用。将来， 根据本研究中产生的证据，有一天可能会使用简单的 d3-肌酸稀释测试 临床上识别肌肉质量低的癌症患者进行干预措施以减轻化学毒性， 心脏代谢风险、功能障碍和死亡率。