外周血指标动态变化与晚期非小细胞肺癌患者对 PD-1 抑制剂联合治疗反应及生存的关系。
Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer.
机构信息
The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China.
Key Hematological of Medical Science and Hematological Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China.
出版信息
Front Immunol. 2021 May 14;12:672271. doi: 10.3389/fimmu.2021.672271. eCollection 2021.
BACKGROUND
PD-1 inhibitors have been routinely used in the treatment of advanced non-small cell lung cancer (NSCLC), and have demonstrated to significantly improve survivorship when combining with other conventional therapies, such as chemotherapy and anti-angiogenesis therapy. PD-L1 is the most commonly used biomarker to select benefiting groups, while not all patients with high PD-L1 expression benefit from immunotherapy. Therefore, identifying other prognostic and predictive biomarkers, including peripheral blood indexes, is essential.
METHODS
We retrospectively collected medical records and hematological data of 151 patients with advanced NSCLC treated with PD-1 inhibitor-based combination therapy in our hospital. The peripheral blood indexes of interest were NLR, PLR, PAR, Hb, LDH, CEA, and NSE. The association between peripheral blood indexes and treatment responses or survival outcomes was examined by multivariable logistic regression and Cox regression, respectively.
RESULTS
The decreased CEA at week 6 (OR = 4.209, 95%CI: 1.287-13.758) or 12 (OR = 7.267, 95%CI: 1.508-35.006) post-treatment was related to a higher disease control rate. The decrease or NLR at week 6 (OR = 3.081, 95%CI: 1.464-6.483) or 12 (OR = 3.304, 95%CI: 1.560-7.001) post-treatment, or CEA at week 12 post-treatment (OR = 2.469, 95%CI: 1.134-5.375), was associated with a higher objective response rate. Patients whose NLR (HR = 0.610, 95%CI: 0.411-0.907) or CEA (HR = 0.477, 95%CI: 0.320-0.710) decreased at week 6 post-treatment tended to have longer progression-free survival, and similar results were found in those with decreased NLR (HR = 0.587, 95%CI: 0.388-0.886) or CEA (HR = 0.406, 95%CI: 0.270-0.609) at week 12 post-treatment. Patients whose CEA (HR = 0.543, 95%CI: 0.339-0.871) or NSE (HR = 0.619, 95%CI: 0.386-0.994) decreased after 6 weeks post-treatment appeared to have longer overall survival, and the same was found for those whoseCEA (HR = 0.620, 95%CI: 0.390-0.986) or NSE (HR = 0.578, 95%CI: 0.353-0.947) was decreased at 12 weeks after treatment.
CONCLUSION
Post-treatment NLR, CEA and NSE changes are suggestive indicators for the prognosis of NSCLC patients after immunotherapy.
背景
PD-1 抑制剂已常规用于治疗晚期非小细胞肺癌（NSCLC），并已证明与其他常规疗法（如化疗和抗血管生成疗法）联合使用时可显著提高生存率。PD-L1 是最常用的生物标志物来选择受益群体，但并非所有高 PD-L1 表达的患者都能从免疫治疗中获益。因此，识别其他预后和预测生物标志物，包括外周血指标，是至关重要的。
方法
我们回顾性收集了我院 151 例接受 PD-1 抑制剂联合治疗的晚期 NSCLC 患者的病历和血液学数据。感兴趣的外周血指标包括 NLR、PLR、PAR、Hb、LDH、CEA 和 NSE。采用多变量逻辑回归和 Cox 回归分别检验外周血指标与治疗反应或生存结局的相关性。
结果
治疗后第 6 周（OR=4.209，95%CI：1.287-13.758）或第 12 周（OR=7.267，95%CI：1.508-35.006）时 CEA 降低与较高的疾病控制率相关。治疗后第 6 周（OR=3.081，95%CI：1.464-6.483）或第 12 周（OR=3.304，95%CI：1.560-7.001）时 NLR 或 NLR 降低，或治疗后第 12 周时 CEA（OR=2.469，95%CI：1.134-5.375）降低与较高的客观缓解率相关。治疗后第 6 周（HR=0.610，95%CI：0.411-0.907）或第 12 周（HR=0.477，95%CI：0.320-0.710）时 NLR 或 CEA 降低的患者无进展生存期更长，且治疗后第 6 周（HR=0.587，95%CI：0.388-0.886）或第 12 周（HR=0.406，95%CI：0.270-0.609）时 NLR 或 CEA 降低的患者也有相似的结果。治疗后第 6 周（HR=0.543，95%CI：0.339-0.871）或第 12 周（HR=0.619，95%CI：0.386-0.994）时 CEA 或 NSE 降低的患者总生存期更长，治疗后第 6 周（HR=0.620，95%CI：0.390-0.986）或第 12 周（HR=0.578，95%CI：0.353-0.947）时 CEA 或 NSE 降低的患者也有相似的结果。
结论
治疗后 NLR、CEA 和 NSE 的变化是预测 NSCLC 患者免疫治疗后预后的提示性指标。
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