肺癌骨转移免疫治疗与非免疫治疗的临床疗效比较

Comparative study of clinical efficacy between immunotherapy and non immunotherapy for bone metastasis of lung cancer

目的探讨免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)伴骨转移的疗效,及ICIs免疫治疗的影响因素,为改善晚期NSCLC骨转移患者预后、指导个体化治疗提供临床依据。方法回顾性分析2019年1月1日—2022年3月31日期间在福建省立医院收治的NSCLC合并骨转移患者的临床资料[性别、发病年龄、吸烟史、骨转移灶情况、病理类型、治疗方案、疗效、无进展生存期(progression free survival,PFS)、总生存期(overall survival,OS)等],随访取得患者的生存资料,运用生存分析(KaplanMeier生存时间曲线)评价ICIs的疗效,以单因素分析(Log-Rank)、多因素分析(Cox回归模型)预测影响ICIs疗效的因素。结果纳入168例NSCLC骨转移患者,有84例接受ICIs治疗,1年生存率为71.43%(60/84),客观缓解率23.81%,疾病控制率84.52%。ICIs治疗组的中位无进展生存期(mid progression free survival,MPFS)为11.0个月(P=0.018),中位生存期(median survival time,MST)为18.3个月(P=0.045),差异有统计学意义。单因素分析显示,发病年龄<65岁(P=0.040)、初诊时美国东部肿瘤协作组体能状态评分标准(Eastern Cooperative Oncology Group Performance Status,ECOG-PS)评分≤1分(P=0.006)、无其他器官转移(P=0.001)、全身化疗(P=0.006)、免疫联合治疗(P=0.012)有更长的PFS;初诊时ECOG-PS≤1分(P=0.043)、无其他器官转移(P=0.001)、全身化疗(P=0.034)有更长的OS;多因素分析显示,发病年龄≥65岁患者的PFS、OS(P=0.012;P=0.002)低于发病年龄<65岁的患者;骨改良药物治疗患者的PFS、OS均明显高于无骨改良药物治疗的患者(P=0.050;P=0.035);伴其他器官转移患者的PFS、OS均明显低于无其他器官转移的患者(P=0.001;P=0.001);初诊时ECOG PS评分≥2分患者的PFS(P=0.047)明显短于初诊时ECOG-PS评分≤1分患者的PFS。结论ICIs明显延长NSCLC骨转移患者的PFS、OS;年龄越小(<65岁)、体能状态良好(ECOG-PS评分≤1分)、无其他器官转移、免疫联合化疗的患者使用ICIs治疗效果更好;年龄越大(≥65岁)、体能状态偏差(ECOG-PS评分≥2分)、伴其他器官转移是肺癌骨转移患者使用ICIs免疫治疗病程进展的独立危险因素,并且发病年龄、伴其他器官转移是ICIs免疫治疗OS的独立预测因子,而骨改良药物骨治疗是NSCLC骨转移患者使用ICIs免疫治疗PFS、OS的独立保护因素。

Objective:To explore the efficacy of immune checkpoint inhibitors(ICIs)on patients with non-small cell lung cancer(NSCLC)and complicated with bone metastases,and the influencing factors of ICIs immunotherapy,in order to provide clinical basis for improving prognosis of patients with advanced NSCLC bone metastases and guiding individualized treatment.Methods:Clinical data of 168 patients with NSCLC complicated with bone metastasies admitted to Fujian Provincial Hospital from January 1,2019 to March 31,2022 were retrospectively analyzed[including gender,age,smoking history,bone metastasies,pathological types,skeletal related events(SREs),treatment plan,efficacy,progression-free survival(PFS),overall survival(OS)etc.],survival data of patients were obtained during follow-up.Survival analysis(Kaplan-Meier survival time curve)was used to evaluate the efficacy of ICIs,and univariate analysis(Log-Rank test)and multivariate analysis(COX regression model)were used to predict the factors affecting the efficacy of ICIs.Results:Of the 168 patients with NSCLC bone metastasis,84 received ICIs.The 1-year survival rate was 71.43%(60/84),the objective remission rate was 23.81%,and the disease control rate was 84.52%.The median progression-free survival(MPFS)was 11.0 months(P=0.018),and the median survival time(MST)was 18.3 months(P=0.045)in the ICIs treatment group.The difference was statistically significant.Univariate analysis showed the age of onset<65 years(P=0.040),ECOG PS≤1 point at the initial diagnosis(P=0.006),no other organ metastasis(P=0.001),systemic chemotherapy(P=0.006),and that combined immunotherapy(P=0.012)had longer PFS;at the initial diagnosis,ECOG PS≤1 point(P=0.043),no other organ metastasis(P=0.001),and that systemic chemotherapy(P=0.034)had longer OS;Multivariate analysis showed that the PFS and OS(P=0.012;P=0.002)of patients with onset age≥65 years were lower than those of patients with onset age<65 years;the PFS and OS of patients treated with bone modifying drugs were significantly higher than those without bone modifying drugs(P=0.050;P=0.035);the PFS and OS of patients with other organ metastasis were significantly lower than those without other organ metastasis(P=0.001;P=0.001);the PFS of patients with ECOG PS score≥2 at initial diagnosis(P=0.047)was significantly shorter than the PFS of patients with ECOG PS score≤1 at initial diagnosis.Conclusion:ICIs significantly prolong PFS and OS in patients with bone metastases from NSCLC;patients with younger age(<65 years old),good physical fitness(ECOG PS≤1 point),no other organ metastasis,and immuno chemotherapy combined with ICIs have better therapeutic effects;older age(≥65 years old),deviation in physical status(ECOG PS≥2 points),accompanied by other organ metastases,and the progression of patients with bone metastases from lung cancer using ICIs immunotherapy are independent risk factors.Moreover,age at onset,accompanied by other organ metastases are independent predictors of the prognosis of OS after ICIs immunotherapy,while bone modification drug bone therapy is an independent protective factor for PFS and OS in patients with bone metastases from NSCLC treated with ICIs immunotherapy.