粒-巨噬细胞集落刺激因子联合立体定向放疗治疗局部晚期或寡转移非小细胞肺癌的临床疗效观察

Clinical Efficacy of GM-CSF Combined with Stereotactic Body Radiotherapy in Treatment of Patients with Locally Advanced or Oligometastatic Non-Small Cell Lung Cancer

[目的]研究粒-巨噬细胞集落刺激因子(GM-CSF)联合立体定向放疗(SBRT)治疗二线及以上的局部晚期或寡转移非小细胞肺癌(NSCLC)的疗效及不良反应。[方法]入组75例适合SBRT、二线及以上的不可手术的ⅢA~ⅣA期NSCLC患者,随机分为单纯SBRT组36例和SBRT+GM-CSF组39例,其中40例患者后续接受了免疫检查点抑制剂(ICI)治疗(SBRT+GM-CSF组18例、SBRT组22例),分析患者的无进展生存期(PFS)和治疗相关不良反应。[结果]SBRT+GM-CSF组PFS显著长于SBRT组,中位PFS分别为8.3个月和6.3个月(P=0.029)。进一步根据患者后续是否进行ICI治疗进行分层分析,结果提示ICI+GM-CSF+SBRT联合治疗组患者的PFS最长,中位PFS达12.3个月。75例患者中,4例患者出现3级及以上不良反应,各组间3级及以上不良反应发生率差异无统计学意义(P>0.05)。[结论]GM-CSF联合SBRT治疗ⅢA~ⅣA期NSCLC较单纯SBRT可显著延长PFS,在此基础上联合ICI治疗能进一步提高疗效。GM-CSF、ICI治疗和SBRT在治疗局部晚期或寡转移NSCLC时有明显的协同增效作用。

[Objective]To investigate the efficacy and adverse reactions of granulocyte-macrophage colony-stimulating factor(GM-CSF)combined with stereotactic body radiotherapy(SBRT)in the treatment of patients with locally advanced or oligometastatic non-small cell lung cancer(NSCLC).[Methods]Seventy-five patients with inoperable stageⅢA~ⅣA NSCLC were randomly assigned in two groups:36 cases received SBRT alone(SBRT group)and 39 cases received SBRT combined GM-CSF(SBRT+GM-CSF group),subsequently 22 cases in SBRT group and 18 cases in SBRT+GM-CSF group were also treated with immunocheckpoint inhibitor(ICI).The progression free survival(PFS)and treatment related adverse reactions were analyzed.[Results]The median PFS of SBRT+GM-CSF group was significantly higher than that of SBRT group(8.3 months vs 6.3 months,P=0.029).Further stratified analysis showed that the patients treated with ICI+GM-CSF+SBRT had the longest PFS,with a median PFS of 12.3 months.Among the 75 patients,4 had≥grade 3 adverse reactions.There was no significant difference in the rate of≥grade 3 adverse reactions among the groups(P>0.05).[Conclusion]GM-CSF combined with SBRT in the treatment of stageⅢA~ⅣA NSCLC can significantly prolong PFS compared with SBRT alone;and additional ICI treatment can further improve the efficacy without increasing adverse reactions.