Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.
目的： 探讨外周血炎症指标对晚期非小细胞肺癌合并慢性阻塞性肺疾病（NSCLC-COPD）患者免疫治疗疗效的影响。 方法： 回顾性分析2019年1月至2021年8月在陆军军医大学新桥医院接受至少2次免疫治疗的178例Ⅲ、Ⅳ期NSCLC-COPD患者资料，收集治疗前2周内白细胞介素6（IL-6）、IL-8、肿瘤坏死因子α（TNF-α）等基线血液检测指标。随访截至2022年2月7日。应用X-tile软件确定外周血炎症指标的cut-off值，采用多因素Cox回归模型分析无进展生存时间（PFS）和总生存时间（OS）的影响因素。 结果： 178例患者中，男174例（97.8%），女4例（2.2%）；年龄42~86（64.3±8.3）岁；免疫单药治疗30例（16.9%），免疫联合化疗治疗114例（64.0%），免疫联合抗血管治疗21例（11.8%），免疫联合放疗13例（7.3%）。中位随访时间为14.5个月（95%CI：13.6~15.3个月）。客观缓解率（ORR）为44.9%（80/178），疾病控制率（DCR）为90.4%（161/178），中位PFS为14.6个月（95%CI：11.6~17.6个月），中位OS为25.7个月（95%CI：18.0~33.4个月）。多因素Cox风险模型分析结果显示，IL-6>9.9 ng/L（HR=5.885，95%CI：2.558~13.543，P<0.01）、TNF-α>8.8 ng/L（HR=3.213，95%CI：1.468~7.032，P=0.003）、IL-8>202 ng/L（HR=2.614，95%CI：1.054~6.482，P=0.038）、全身免疫炎症指数（SII）>2 003.95（HR=2.976，95%CI：1.647~5.379，P<0.001）是PFS的危险因素，晚期肺癌炎症指数（ALI）>171.15是PFS的保护因素（HR=0.545，95%CI：0.344~0.863，P=0.010）；IL-6>9.9 ng/L（HR=6.124，95%CI：1.950~19.228，P<0.002）、乳酸脱氢酶（LDH）>190.7 U/L（HR=2.776，95%CI：1.020~7.556，P=0.046）、SII>2 003.95（HR=4.521，95%CI：2.241~9.120，P<0.001）是OS的危险因素，ALI>171.15是OS的保护因素（HR=0.434，95%CI：0.243~0.778，P=0.005）。 结论： 基线高水平IL-6、TNF-α、IL-8、SII、LDH和低水平ALI是接受免疫治疗晚期NSCLC-COPD患者预后不良的危险因素。.