Thoracic Oncology Unit, University Hospital of Montpellier, Arnaud de Villeneuve Hospital, 371 avenue Doyen Gaston Giraud, 34295, Montpellier, France; Cancerology Resarch Institute of Montpellier (IRCM), INSERM unit-U1194, 208 avenue des Apothicaires, 34298, Montpellier, France.
Laboratory of Biostatistics and Epidemiology, University Institute for Clinical Research, Montpellier, France.
Lung Cancer. 2020 May;143:19-26. doi: 10.1016/j.lungcan.2020.03.003. Epub 2020 Mar 5.
The metabolic changes associated with cachexia - sarcopenia syndrome might down-regulate antitumor immunity. We hypothesized that this syndrome reduces efficiency of immune checkpoint inhibitors (ICPI) in non-small cell lung cancer (NSCLC).
The records of 142 consecutive NSCLC patients receiving first- or second-line anti-Programmed cell death protein 1) ICPI were reviewed. Response evaluation according to Response Evaluation Criteria in Solid Tumors 1.1 was performed at the eighth week of immunotherapy. Pretreatment cachexia was defined as a body-weight loss of 5% or more in the previous 6 months. Sarcopenia was estimated with the third lumbar skeletal muscle mass index (mSMI) and was evaluated before immunotherapy and at the eighth week. A decrease by 5% or more of the mSMI was considered as an evolving sarcopenia. The endpoints were disease control rate (DCR), progression-free (PFS) and overall survival (OS).Logistic regression model and Cox model took into account others covariables known to influence ICPI efficiency, particularly Programmed Death -Ligand 1 tumor cell score, Eastern Cooperative Oncology Group performance status and common somatic mutational status.
In multivariate analysis, cachexia - sarcopenia syndrome reduced the probability of achieving a disease control and were associated with a shorter survival. Patients without cachexia had a better probability to achieve disease control in comparison with those who did not experience cachexia (59.9 % and 41.1 %, respectively; odds ratio 95 % (confidence interval [95 %CI]): 2.60 (1.03-6.58)). Patients with cachexia had a shorter OS when compared with those without cachexia (hazard ratios [HR] (95 %CI): 6.26 (2.23-17.57)). Patients with an evolving sarcopenia had a shorter PFS and OS, with HR (95 %CI): 2.45 (1.09-5.53) and 3.87 (1.60-9.34) respectively.
Cachexia - sarcopenia syndrome negatively influences patients' outcome during anti-PD-1 ICPI therapy.
恶病质-肌少症综合征相关的代谢变化可能会下调抗肿瘤免疫。我们假设该综合征会降低非小细胞肺癌（NSCLC）患者免疫检查点抑制剂（ICPI）的疗效。
回顾了 142 例连续接受一线或二线抗程序性细胞死亡蛋白 1（PD-1）ICPI 的 NSCLC 患者的记录。根据实体瘤反应评估标准 1.1 在免疫治疗的第 8 周进行疗效评估。治疗前恶病质定义为过去 6 个月体重下降 5%或更多。通过第 3 腰椎骨骼肌质量指数（mSMI）来评估肌少症，并在免疫治疗前和第 8 周进行评估。mSMI 下降 5%或更多被认为是进行性肌少症。终点是疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。逻辑回归模型和 Cox 模型考虑了其他已知影响 ICPI 疗效的协变量，特别是程序性死亡配体 1 肿瘤细胞评分、东部肿瘤协作组表现状态和常见体细胞突变状态。
多变量分析表明，恶病质-肌少症综合征降低了疾病控制的可能性，并与较短的生存期相关。无恶病质的患者比有恶病质的患者更有可能实现疾病控制（分别为 59.9%和 41.1%；优势比 95%置信区间[95%CI]：2.60[1.03-6.58]）。与无恶病质的患者相比，有恶病质的患者 OS 更短（风险比[HR]（95%CI）：6.26[2.23-17.57]）。进行性肌少症患者的 PFS 和 OS 更短，HR（95%CI）分别为 2.45[1.09-5.53]和 3.87[1.60-9.34]。
恶病质-肌少症综合征对抗 PD-1 ICPI 治疗期间患者的结局产生负面影响。
