Balstad Trude R, Brunelli Cinzia, Pettersen Caroline H, Schønberg Svanhild A, Skorpen Frank, Fallon Marie, Kaasa Stein, Bye Asta, Laird Barry J A, Stene Guro B, Solheim Tora S
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Front Nutr. 2021 Jan 14;7:602775. doi: 10.3389/fnut.2020.602775. eCollection 2020.
New clinical trials in cancer cachexia are essential, and outcome measures with high responsiveness to detect meaningful changes are crucial. This secondary analysis from a multimodal intervention trial estimates sensitivity to change and between treatment effect sizes (ESs) of outcome measures associated with body composition, physical function, metabolism, and trial intervention. The study was a multicenter, open-label, randomized pilot study investigating the feasibility of a 6-week multimodal intervention [exercise, non-steroidal anti-inflammatory drugs, and oral nutritional supplements containing polyunsaturated fatty acids (-3 PUFAs)] vs. standard cancer care in non-operable non-small-cell lung cancer and advanced pancreatic cancer. Body composition measures from computerized tomography scans and circulating biomarkers were analyzed. Forty-six patients were randomized, and the analysis included 22 and 18 patients in the treatment and control groups, respectively. The between-group ESs were high for body weight (ES = 1.2, < 0.001), small for body composition and physical function [handgrip strength (HGS)] measures (ES < 0.25), moderate to high for n-3 PUFAs and 25-hydroxyvitamin D (25-OH vitamin D) (ES range 0.64-1.37, < 0.05 for all), and moderate for serum C-reactive protein (ES = 0.53, = 0.12). Analysis within the multimodal treatment group showed high sensitivity to change for adiponectin (ES = 0.86, = 0.001) and n-3 PUFAs (ES > 0.8, < 0.05 for all) and moderate for 25-OH vitamin D (ES = 0.49, = 0.03). In the control group, a moderate sensitivity to change for body weight (ES = -0.84, = 0.002) and muscle mass (ES = -0.67, = 0.016) and a high sensitivity to change for plasma levels of 25-OH vitamin D (ES = -0.88, = 0.002) were found. Demonstrating high sensitivity to change and between treatment ES and body composition measures, body weight still stands out as a clinical and relevant outcome measure in cancer cachexia. Body composition and physical function measures clearly are important to address but demand large sample sizes to detect treatment group differences. ClinicalTrials.gov identifier: NCT01419145.
开展针对癌症恶病质的新临床试验至关重要，而具备高反应性以检测有意义变化的结局指标至关重要。这项来自多模式干预试验的二次分析评估了与身体成分、身体功能、代谢及试验干预相关的结局指标对变化的敏感性以及治疗效果大小（ES）之间的差异。该研究是一项多中心、开放标签、随机对照的试点研究，旨在探究为期6周的多模式干预（运动、非甾体抗炎药以及含多不饱和脂肪酸的口服营养补充剂（-3多不饱和脂肪酸））与非手术不可切除的非小细胞肺癌和晚期胰腺癌的标准癌症治疗相比的可行性。分析了计算机断层扫描的身体成分测量结果以及循环生物标志物。46例患者被随机分组，分析分别纳入了治疗组的22例患者和对照组的18例患者。体重的组间ES较高（ES = 1.2，< 0.001），身体成分和身体功能[握力（HGS）]测量指标的ES较小（ES < 0.25），n-3多不饱和脂肪酸和25-羟基维生素D（25-OH维生素D）的ES为中度至高度（ES范围为0.64 - 1.37，均< 0.05），血清C反应蛋白的ES为中度（ES = 0.53，= 0.12）。多模式治疗组内分析显示，脂联素（ES = 0.86，= 0.001）和n-3多不饱和脂肪酸（ES > 0.8，均< 0.05）对变化的敏感性较高，25-OH维生素D的敏感性为中度（ES = 0.49，= 0.03）。在对照组中，发现体重（ES = -0.84，= 0.002）和肌肉量（ES = -0.67，= 0.016）对变化的敏感性为中度，血浆25-OH维生素D水平对变化的敏感性较高（ES = -0.88，= 0.002）。体重在显示对变化及治疗组间ES和身体成分测量的高敏感性方面，在癌症恶病质中仍是突出的临床相关结局指标。身体成分和身体功能测量指标显然很重要，但需要大样本量才能检测到治疗组间差异。ClinicalTrials.gov标识符：NCT01419145。
