目的 探讨肌肉减少症对预测使用程序性死亡受体 1 / 程序性死亡配体 1(PD-1 / PD-L1)免疫检查点抑制剂(ICIs) 治疗的局部晚期或转移性非小细胞肺癌(NSCLC)患者预后以及免疫相关性不良反应( irAEs)发生率的应用价值。 方法 本研 究为回顾性研究。 选取 2019 年 5 月 1 日至 2022 年 4 月 30 日期间就诊于南京医科大学附属苏州医院接受一线、二线或三线 ICIs 治疗的 82 例局部晚期或转移性 NSCLC 患者。 根据骨骼肌质量指数( SMI) 将患者分为肌肉减少症组和非肌肉减少症 组,收集患者的 SMI、血常规、生化、治疗反应等随访数据,通过 Kaplan-Meier 曲线、Cox 比例风险回归模型、Mann-Whitney U 检 验、卡方检验、单多因素 Logistics 回归分析、独立 t 检验等方法评估肌肉减少症对预测局部晚期或转移性 NSCLC 患者接受 PD-1 / PD-L1 抑制剂治疗疗效的价值。 结果 82 例入选患者的中位无进展生存(PFS) 期为 8. 5 个月(范围 0. 7 ~ 40 个月, 95%CI = 8. 16~ 11. 47)。 通过 Kaplan-Meier 曲线分析发现,肌肉减少症组的 PFS 期明显短于非肌肉减少症组(5. 8 个月比 10 个月,P= 0. 017)。 通过 Mann-Whitney U 检验发现,甘油三酯、腰围、Karnofsky 功能状态(KPS)评分、营养风险筛查 2002(NRS 2002)量表评分在两组患者中有明显差异(分别为 P = 0. 022、0. 004、0. 009、0. 007),两组的客观缓解率(ORR) 有显著差异 (5. 56%比 39. 13%,P= 0. 001)。 根据患者是否发生疾病缓解,将患者分为完全缓解+部分缓解组(即 OR 组)和疾病稳定+疾 病进展组(即非 OR 组),通过独立 t 检验发现,OR 组和非 OR 组的 SMI 有显著差异[(50. 24±8. 48) cm 2 / m 2 比(45. 09±9. 82) cm 2 / m 2 ,P= 0. 0408],肌肉减少症组 irAEs 发生率明显高于非肌肉减少症组(P = 0. 015),且 irAEs 与体质指数(BMI)、白球比 (A/ G)、甘油三酯、腰围、三线治疗、肌肉减少症相关,其中 A/ G 和三线治疗是独立危险因素。 结论 肌肉减少症可作为预测接受 PD-1 / PD-L1 治疗的局部晚期或转移性 NSCLC 患者预后的敏感指标,能有效地识别预后不良患者,进而提供更为详尽的 预后分层,有效指导临床提前干预。

Objective To investigate the value of sarcopenia in predicting the prognosis of advanced NSCLC patients using PD1 / PD-L1 immune checkpoint inhibitors ICIs and the incidence of immune - related adverse events irAEs . Method A total of 82 eligible patients with advanced NSCLC treated by PD1 / PD-L1 inhibitors in first-line second-line or third-line were enrolled from May 1 2019 to April 30 2022 at the affiliated Suzhou Hospital of Nanjing Medical University. Patients were divided into sarcopenia group and non- sarcopenia group based on SMI. All the follow - up data including skeletal muscle index SMI blood routine examination blood biochemical test and treatment response were collected in the electronic medical record system. Through Kaplan-Meier Cox survival analysis the Mann - Whitney U test the chi square test univariate and multiple Logistic regression analysis and an independent t-test we evaluated the value of sarcopenia in predicting the curative effect of ICI inhibitors for patients with advanced NSCLC. Result The median progression free survival PFS of all 82 enrolled patients was 8. 5 months range 0. 7-40 months 95%CI = 8. 16-11. 47 . The Kaplan-Meier analysis revealed that patients with sarcopenia had a significantly shorter PFS than those without sarcopenia 5. 8 vs 10 months P = 0. 017 . Mann-Whitney U test showed that triglyceride waist circumference nutritional risk screening 2002 NRS 2002 grade and Karnofsky performance score KPS were significantly different between the two groups P= 0. 022 0. 004 0. 009 0. 007 respectively . Patients were grouped according to whether they had an objective response,and it was found by independent t - test. There was a significant difference in ORR between the sarcopenia group and the non - sarcopenia group 5. 56% vs 39. 13% P = 0. 001 . Based on the occurrence of disease remission patients were categorized into a group of complete remission and partial remission referred to as the OR group and a group of stable disease and disease progression referred to as the non-OR group . An independent t-test revealed a significant difference in SMI between the OR group and the non-OR group 50. 24±8. 48 cm 2 / m 2 vs 45. 09±9. 82 cm 2 / m 2 P= 0. 0408 . The incidence of irAEs in the sarcopenia group was higher than the non-sarcopenia group P= 0. 015 . Moreover irAEs were associated with body mass index BMI albumin / globulin ratio A/ G triglyceride waist circumference third-line treatment and sarcopenia among which A/ G and third-line treatment were independent risk factors. Conclusion Sarcopenia can be used as a sensitive indicator to predict the prognosis of patients with advanced NSCLC receiving immunotherapy. It can effectively identify patients with a poor prognosis thus providing more detailed prognosis stratification and effectively guide clinical early intervention.