【摘要】 目的 观察扶正方药治疗三线及以上晚期非小细胞肺癌（NSCLC）患者的疗效及对血清可溶性免疫检查点表达的影响。方法 根据治疗情况将211例三线及以上晚期NSCLC患者分为暴露组（106例）、非暴露组（105例），非暴露组给予标准西医治疗方案，暴露组在标准西医治疗方案的基础上加用中医扶正方药。观察无进展生存期（PFS），绘制Kaplan-Meier生存曲线，对临床因素及预后指标进行Cox多因素分析；治疗4个周期后计算疾病控制率，比较生活质量量表[癌症患者生活质量核心问卷量表（QLQ-C30）、肺癌特异性量表（QLQ-LC13）]评分、血清可溶性免疫检查点[包括可溶性CD137(sCD137)、可溶性程序性细胞死亡配体1(sPD-L1)、可溶性程序性细胞死亡配体2(sPD-L2)、可溶性程序性死亡分子-1(sPD-1)、可溶性淋巴细胞激活基因-3蛋白（sLAG-3）、可溶性半乳糖凝集素-9(sGal-9)等]表达水平的变化情况。结果 (1)暴露组脱落2例、非暴露组脱落1例，最终完成试验者208例，暴露组、非暴露组各104例。(2)暴露组、非暴露组的中位PFS分别为7.5个月、6.3个月，暴露组PFS长于非暴露组（χ~2=4.656,P<0.05）；与非暴露组相比，暴露组PFS缩短的风险降低了22.8%。(3)暴露组、非暴露组疾病控制率分别为85.6%、79.8%；两组疾病控制率比较，差异无统计学意义（P>0.05）。(4)治疗前后组内比较，暴露组QLQ-C30量表中躯体功能、情绪功能、认知功能和总健康状况、疲倦、疼痛、气促、失眠、食欲、便秘、腹泻评分差异有统计学意义（P<0.05）,QLQ-LC13量表中气促、咳嗽、口腔溃疡、其他部位痛评分降低（P<0.05）；非暴露组QLQ-C30量表中躯体功能、社会功能、疼痛、气促、便秘、腹泻评分差异有统计学意义（P<0.05）,QLQ-LC13量表中气促、咳嗽评分降低（P<0.05），其他部位痛评分升高（P<0.05）。组间治疗后比较，QLQ-C30量表中躯体功能、总健康状况、疲倦、疼痛、气促、食欲、便秘评分差异有统计学意义（P<0.05）,QLQ-LC13量表中气促、咳嗽、口腔溃疡及其他部位痛评分差异有统计学意义（P<0.05）。(5)治疗前后组内比较，暴露组血清sPD-L1、sPD-L2水平降低，sPD-1、sGal-9水平升高（P<0.05）；组间治疗后比较，sCD137、sPD-L1、sPD-L2、sLAG-3水平差异有统计学意义（P<0.05）。结论 与单纯使用西医治疗相比，加用扶正方药治疗三线及以上晚期NSCLC患者具有延长PFS、改善生活质量、调节免疫微环境等作用。更多还原

【Abstract】 Objective To observe the efficacy of Fuzheng Formula in the third-line and beyond treatment for advanced non-small cell lung cancer(NSCLC) and its impact on the expressions of serum soluble immune checkpoints.Methods A total of 211 patients with advanced NSCLC undergoing the third-line or beyond treatment were divided into an exposed group (n=106) receiving Fuzheng Formula in addition to standard Western medical treatment,and a non-exposed group (n=105) receiving only the standard Western medical treatment.Progression-free survival(PFS) was observed,Kaplan-Meier survival curves were drawn,and clinical factors and prognostic indicators were analyzed using Cox multivariate analysis.The disease control rate was calculated after four treatment cycles.Quality of life scores[assessed using the Quality of Life Questionnare-Core 30 (QLQ-C30) and Quality of Life Questionnare-Lung Cancer 13 (QLQ-LC13)],and changes in the levels of serum soluble immune checkpoints[including soluble CD137 (sCD137),soluble programmed cell death ligand 1 (sPD-L1),soluble programmed cell death ligand 2 (sPD-L2),soluble programmed death molecule-1 (sPD-1),soluble lymphocyte-activated gene-3 protein (sLAG-3),and soluble galactose lectin-9 (sGal-9)]were compared.Results①Two cases in the exposed group and one case in the non-exposed group dropped out,and 208 cases finally completed the trial with 104 cases in each group.②The median PFS of the exposed and non-exposed groups were 7.5months and 6.3 months,respectively,with the exposed group showing a significantly longer PFS（χ~2=4.656,P<0.05) and a 22.8%reduced risk of PFS progression.③The disease control rates of the exposed and non-exposed groups were 85.6%and 79.8%,respectively,with no significant difference between two groups (P>0.05）.④Intra-group comparisons before and after treatment showed significant differences in QLQ-C30 scale scores for somatic functioning,emotional functioning,cognitive functioning and total health,fatigue,pain,shortness of breath,insomnia,appetite,constipation,and diarrhea in the exposed group (P<0.05);and the QLQ-LC13 scale scores for shortness of breath,coughing,mouth ulcers,and other parts of the body pain were reduced in the exposed group (P<0.05).In the non-exposed group,significant differences were observed after treatment in QLQ-C30 scale scores for somatic functioning,social functioning,pain,shortness of breath,constipation,and diarrhea (P<0.05);and the QLQ-LC13 scale scores for shortness of breath,coughing were reduced (P<0.05),scale score for other parts of the body pain was elevated(P<0.05).Inter-group comparisons post-treatment showed significant differences in QLQ-C30 scale scores for somatic functioning,total health,fatigue,pain,shortness of breath,appetite,and constipation (P<0.05),and in QLQ-LC13 scale scores for shortness of breath,coughing,mouth ulcers,and pain in other parts of the body (P<0.05）.⑤Intra-group comparisons before and after treatment showed that levels of sPD-L1 and sPD-L2decreased,while sPD-1 and sGal-9 levels increased in the exposed group (P<0.05).Inter-group comparisons post-treatment showed significant differences in levels of sCD137,sPD-L1,sPD-L2,and sLAG-3 (P<0.05).Conclusion Compared to the single use of Western medicine for treatment,incorporating Fuzheng Formula in the third-line and beyond treatment for advanced NSCLC has been shown to extend PFS,improve quality of life,and modulate the immune microenvironment.更多还原