CD8+、IL-6和PaO2对不可切除ⅢB/C和Ⅳ期非小细胞肺癌免疫治疗触发放射召回性肺炎的预测价值

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CD8⁺、IL-6和PaO₂对不可切除Ⅲ_B/C和Ⅳ期非小细胞肺癌免疫治疗触发放射召回性肺炎的预测价值

Predictive value of CD8⁺, IL-6, and PaO₂ for immunotherapy-triggered radiation recall pneumonitis in unresectable stage Ⅲ_B/C and IV non-small cell lung cancer

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doi:10.6040/j.issn.1671-7554.0.2024.0832

摘要： 目的探讨不可切除的Ⅲ_B/C和Ⅳ期巩固性放疗的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者在接受免疫检查点抑制剂(immune checkpoint inhibitors, ICI)治疗后,能够触发患者并发放射召回性肺炎(radiation recall pneumonitis, RRP)的预测指标。方法回顾性分析青岛市市立医院2020年3月至2023年11月间放疗后序贯ICI治疗的不可切除Ⅲ_B/C和Ⅳ期巩固性放疗的NSCLC患者,分为RRP组和非RRP组。收集患者临床信息,包括性别、年龄、体质量指数、体能状态评分、TNM分期、平均肺剂量(mean lung dose, MLD)、V20、血压、FEV₁、FVC、FEV₁/FVC 、PaO₂、PaCO₂、降钙素原、白细胞介素6(interleukin-6, IL-6)、外周血CD4⁺及CD8⁺T细胞计数,以Logistic回归分析与ROC特征分析结果评估危险因素。结果此研究共收集到患者55例,包括非RRP组30例(54.45%)、RRP组25例(45.45%),其中RRP危重症3例(3/55,5.45%)。两组的性别、年龄、体质量指数、体能状态评分、TNM 分期、MLD、V20、血压、FEV₁、FVC、FEV₁/FVC、PaCO₂、降钙素原、CD4⁺细胞差异均无统计学意义(P>0.05)。RRP组PaO₂(P=0.007)和CD8⁺T细胞计数(P=0.040)低于非RRP组,IL-6 浓度(P<0.001)高于非RRP组。PaO₂和IL-6在单因素和多因素分析中都显示出较高的显著性(P<0.01),CD8⁺T细胞在多因素分析中为较显著因素(P<0.05),ROC曲线AUC值PaO₂>IL-6>CD8⁺T细胞。结论不可切除的Ⅲ_B/C和Ⅳ期NSCLC患者放疗后序贯ICI治疗,RRP发生率高,但RRP危重症发生率低。PaO₂低、IL-6高水平和外周血CD8⁺T细胞计数减少可作为ICI 触发RRP的高风险因素,具有较准确的预测能力。

关键词: 非小细胞肺癌, 免疫检查点抑制剂, 放射召回性肺炎, CD8⁺, 自细胞介素 6

Abstract: Objective To explore predictive markers that can trigger radiation recall pneumonitis(RRP)in patients with unresectable stage Ⅲ_B/C and Ⅳ non-small cell lung cancer(NSCLC)who receive immune checkpoint inhibitors(ICIs)following consolidative radiotherapy. Methods A retrospective analysis was conducted at Qingdao Municipal Hospital on patients with unresectable stage Ⅲ_B/C and IV NSCLC who underwent radiotherapy followed by sequential ICI therapy from March 2020 to November 2023. Patients were divided into RRP and non-RRP groups. Clinical information, including gender, age, body mass index, performance status score, TNM stage, mean lung dose(MLD), V20, blood pressure, FEV₁, FVC, FEV₁/FVC, PaO₂, PaCO₂, procalcitonin, interleukin-6(IL-6), peripheral blood CD4⁺ and CD8⁺ T-cell counts were collected and assessed through Logistic regression and ROC curve analysis to evaluate risk factors. Results A total of 55 patients were included, with 30 in the non-RRP group(54.45%)and 25 in the RRP group(45.45%), including 3 critical RRP cases(3/55, 5.45%). There were no statistically significant differences between the two groups in terms of gender, age, BMI, performance status score, TNM stage, MLD, V20, blood pressure, FEV₁, FVC, FEV₁/FVC, PaCO₂, procalcitonin, and CD4⁺ cell counts(P>0.05). The RRP group had significantly lower PaO₂(P=0.007)and CD8⁺ T-cell counts(P=0.040), and higher IL-6 levels(P<0.001)compared to the non-RRP group. Both PaO₂ and IL-6 showed high significance in univariate and multivariate analyses(P<0.01), while CD8⁺ T-cells were significant in multivariate analysis(P<0.05). In the ROC curve analysis, the AUC values ranked as PaO₂ > IL-6 > CD8⁺ T-cells. Conclusion Patients with unresectable stage Ⅲ_B/C and IV NSCLC undergoing radiotherapy followed by ICIs therapy have a low incidence of critical RRP, though a high incidence of RRP. Low PaO₂, elevated IL-6 levels, and decreased peripheral blood CD8⁺ T-cell counts can serve as high-risk predictors for ICI-triggered RRP, exhibiting considerable predictive accuracy.

Key words: Non-small cell lung cancer, Immune checkpoint inhibitors, Radiation recall pneumonitis, CD8⁺, Interleukin-6

中图分类号:

R734.2

徐年兴,魏东,乔俊杰,战炳炎. CD8⁺、IL-6和PaO₂对不可切除Ⅲ_B/C和Ⅳ期非小细胞肺癌免疫治疗触发放射召回性肺炎的预测价值[J]. 山东大学学报 (医学版), 2025, 63(2): 29-35.

XU Nianxing, WEI Dong, QIAO Junjie, ZHAN Bingyan. Predictive value of CD8⁺, IL-6, and PaO₂ for immunotherapy-triggered radiation recall pneumonitis in unresectable stage Ⅲ_B/C and IV non-small cell lung cancer[J]. Journal of Shandong University (Health Sciences), 2025, 63(2): 29-35.

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