Department of Medical Sciences and Public Health, Medical Oncology Unit, "Azienda Ospedaliero Universitaria" of Cagliari, University of Cagliari, Cagliari, Italy.
Medical Oncology Unit, San Gavino Hospital, San Gavino, Italy.
ESMO Open. 2024 Oct;9(10):103738. doi: 10.1016/j.esmoop.2024.103738. Epub 2024 Oct 10.
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.
瘦素是一种可靠的预测和替代标志物，可预测多靶点治疗癌症恶病质的疗效。
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效果中的预测作用，而这仍然是一个复杂的问题。在此，我们旨在寻找一种能够检测抗恶病质治疗早期反应的标志物。
从 2012 年 1 月至 2022 年 12 月，根据入选标准，所有符合条件的连续晚期癌症恶病质患者均前瞻性纳入探索性和验证性队列。所有患者均接受了包含醋酸甲地孕酮、塞来昔布、左卡尼汀和抗氧化剂的联合抗恶病质治疗，该治疗方案在之前的 III 期随机研究中显示有效。主要终点为增加去脂体重（LBM）、降低静息能量消耗（REE）、降低疲劳感以及改善整体生活质量。
共纳入 553 例连续患者。由于疾病进展导致早期死亡，20 例患者（探索性队列 11 例，验证性队列 9 例）脱落，故 533 例患者被认为可评估。瘦素水平的变化与循环炎症介质水平呈负相关，反映了身体成分、能量代谢、功能表现和生活质量的改善。多元回归分析显示，在第 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；在第 16 周时，瘦素变化是相同参数和 Eastern Cooperative Oncology Group 表现状态改善的独立预测因子。与其他炎症标志物相比，瘦素预测 LBM、SMI、REE 和握力变化的能力更优。此外，增加瘦素差值与 LBM、SMI、REE、握力和疲劳感的改善显著相关。
瘦素是多靶点抗恶病质治疗效果的可靠预测标志物。因此，它可以作为监测和预测抗恶病质治疗效果的理想候选标志物，也是所选药物免疫代谢作用的替代标志物。
