瘦素是癌症恶病质多靶点治疗功效的可靠预测和替代标志物。据我们所知，尚无研究评估生物标志物在确定抗恶病质治疗有效性方面的预测作用，这仍然是一个复杂的问题。在此，我们的目标是找到一种可以检测抗恶病质治疗早期反应的标志物。从2012年1月到2022年12月，所有连续符合资格的恶病质晚期癌症患者根据资格标准前瞻性地纳入探索和验证队列。所有患者均接受了由醋酸甲地孕酮加塞来昔布加左旋肉碱加抗氧化剂组成的联合抗恶病质治疗，该治疗在之前的 III 期随机研究中显示出疗效。主要终点是去脂体重 (LBM) 的增加、静息能量消耗 (REE) 的减少、疲劳的减少以及整体生活质量的改善。总共招募了 553 名连续患者。 20 名患者因疾病进展而过早死亡，平均分布在探索组（11 名患者）和验证组（9 名患者）中退出。然后，533 名患者被认为可以评估。瘦素水平的变化与炎症介质的循环水平呈负相关，反映了身体成分、能量代谢、功能表现和生活质量的改善。在多变量回归分析中，第 8 周时，瘦素变化是 LBM、骨骼肌指数 (SMI)、握力增加和 REE 的独立预测因子；第 16 周时，瘦素变化是东部肿瘤合作组表现状态相同参数和改善的独立预测因子。在比较接受者操作曲线时，瘦素预测 LBM、SMI、REE 和握力变化的能力优于其他炎症标志物。此外，增加 Delta 瘦素值与 LBM、SMI、REE、握力和疲劳的显着改善结果相关。瘦素是多靶点抗恶病质治疗结果的可靠预测标记。因此，它可以成为监测和预测抗恶病质治疗效果的理想候选者，也是所选药物免疫代谢作用的替代标记。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia.To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment.From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life.A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue.Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.