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

摘要 结直肠癌(CRC)是美国第四种最常见的癌症。在临床上使用- 获得性CT扫描测量肌肉横截面积(CSA)，患病率 非转移性结直肠癌患者的下肌率估计为42%。低CT CSA与 化疗毒性风险增加2倍以上，手术并发症风险增加26%和46% 增加特定于结直肠癌的死亡风险。然而，使用CT来估计肌肉质量受到限制，因为 CT并不是所有癌症的标准治疗方法，通常局限于一个解剖区域，无法区分 收缩肌肉蛋白与肌肉筋膜内其他组织之间的相互作用。替代方案包括双能x射线。 吸光度(DXA)，测量所有瘦体重(LBM)，包括纤维组织和结缔组织， 水和器官。然而，DXA和CT都不能直接量化全身肌肉质量，两种方法都不能 让病人暴露在辐射中。安全和非侵入性的肌肉质量评估方法将有助于我们的 了解肌肉丧失可能影响癌症和癌症后的发病率和死亡率的机制 加强干预措施，如针对癌症患者肌肉质量的体力活动。为此，对于 首次在癌症患者中，这项拟议的研究将评估直接和非侵入性的相关性 评估全身肌肉质量的方法和结果。氢化肌酸稀释度(d3-肌酸)估算 总肌酸池大小，从而肌肉质量，使用口服剂量的d3-肌酸和测量d3-肌酐 几天后，在单一的现场尿样中进行浓缩。因为肌酸位于收缩肌内 肌节的组成部分，d3-肌酸稀释度提供了一种功能性肌肉质量的衡量标准。本研究 将在一项随机对照试验中测量90名结肠癌患者的d3-肌酸质量 在已经收集CT CsA和DXA LBM的化疗期间进行耐药性训练。我们 将测试d3-肌酸对阻力训练的反应是否发生变化，并检查d3-肌酸是否 肌酸肌块与功能、代谢、炎症和化疗结果相关。在……里面 此外，我们将比较这种关联的强度与d3-肌酸肌块的结果。 对于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-肌酸稀释将是一个有用的工具 肌肉质量和体力活动干预在癌症患者中的作用研究。在未来， 根据这项研究中产生的证据，简单的d3-肌酸稀释试验有朝一日可能会被使用。 临床上识别肌肉质量低的癌症患者以进行干预以减轻化疗毒性， 心脏代谢风险、功能损害和死亡率。

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.