Medical Oncology, San Salvatore Hospital, University of L'Aquila, L'Aquila, Italy.
Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Sci Rep. 2020 Jan 29;10(1):1456. doi: 10.1038/s41598-020-58498-2.
Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/-25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05-2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31-3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31-3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.
肌肉减少症是所有慢性疾病（包括癌症）的特征之一，在免疫治疗前时代已被作为预后标志物进行研究。可以通过 CT 扫描的横断面图像分析来评估肌肉减少症，在第三腰椎（L3）水平评估骨骼肌指数（SMI），这是骨骼肌质量的替代指标，并评估骨骼肌密度（SMD）。我们对接受 PD-1/PD-L1 检查点抑制剂治疗的连续晚期癌症患者进行了回顾性分析。评估了基线 SMI 和 SMD，并根据性别和 BMI（+/-25）计算了最佳生存截断值。评估的临床结局包括：客观缓解率（ORR）、免疫相关不良事件（irAEs）、无进展生存期（PFS）和总生存期（OS）。从 2015 年 4 月至 2019 年 4 月，评估了 100 例连续的晚期癌症患者。50 例（50%）患者的基线 SMI 较低，而根据既定的截断值，51 例（51%）患者的基线 SMD 较低。我们发现 SMI 与 ECOG-PS 之间存在显著关联（p=0.0324），而 SMD 与基线临床因素之间没有相关性。中位随访时间为 20.3 个月。在单因素分析中，低 SMI 患者的 PFS 明显更短（HR=1.66[95%CI：1.05-2.61]；p=0.0291），但在多因素分析中则不然。他们的 OS 也明显更短（HR=2.19[95%CI：1.31-3.64]；p=0.0026）。多因素分析证实基线 SMI 是 OS 的独立预测因素（HR=2.19[1.31-3.67]；p=0.0027）。我们没有发现基线 SMD 与临床结局之间存在显著关系，也没有发现基线 SMI 与 ORR、irAEs 之间存在显著关系（未显示数据）。在接受 PD1/PDL1 检查点抑制剂治疗的晚期癌症患者中，低 SMI 与生存缩短相关。然而，SMI 与临床反应之间缺乏关联表明，在这种情况下，肌肉减少症可能是总体预后因素，而不是免疫治疗反应的特异性预测因素。
