深部热疗联合信迪利单抗及nab-PC方案治疗驱动基因阴性、PD-L1表达阳性晚期鳞状非小细胞肺癌效果及安全性

Efficacy and safety of deep hyperthermia combined with sintilimab and nab-PC regimen in the treatment of advanced squamous non-small cell lung cancer with driver gene negative and PD-L1 expression positive

目的探讨深部热疗联合信迪利单抗及nab-PC(白蛋白结合型紫杉醇+卡铂)方案治疗驱动基因阴性、程序性死亡受体配体1(PD-L1)表达阳性的晚期鳞状非小细胞肺癌(NSCLC)的临床效果及安全性。方法前瞻性病例对照研究。收集河北省第七人民医院2020年1月至2022年12月收治的84例驱动基因阴性、PD-L1表达阳性的晚期鳞状NSCLC患者。按随机数字表法分为观察组与对照组(各42例)。对照组给予信迪利单抗联合nab-PC方案治疗,观察组在对照组基础上联合深部热疗。连续治疗4个周期后比较两组患者近期疗效,比较两组治疗前后患者血清肿瘤标志物[癌胚抗原(CEA)、鳞状细胞癌抗原(SCCA)、细胞角蛋白片段19(CYFR21-1)]水平以及免疫组织化学标志物[p40、p63、细胞角蛋白5/6(CK5/6)]阳性表达率,比较两组癌症治疗功能评价系统-肺癌模块(FACT-L)评分、不良反应和远期生存情况。结果观察组男性26例,女性16例,年龄(59±11)岁;对照组男性22例,女性15例,年龄(58±11)岁。观察组客观缓解率、疾病控制率分别为71.43%(30/42)、90.48%(38/42),对照组客观缓解率、疾病控制率分别为50.00%(21/42)、80.95%(34/42);观察组客观缓解率高于对照组,差异有统计学意义(χ^(2)=4.04,P=0.044);两组疾病控制率比较差异无统计学意义(χ^(2)=1.56,P=0.212)。治疗后两组血清CEA、SCCA、CYFRA21-1水平以及p40、p63、CK5/6阳性表达率均较治疗前低(均P<0.05),FACT-L评分中生理状况、功能状况、附加关注情况维度评分及量表总分均较治疗前高(均P<0.05)。两组血小板减少、中性粒细胞减少、白细胞减少、贫血、发热等发生率比较差异均无统计学意义(均P>0.05)。观察组和对照组中位无进展生存时间分别为6.5个月(95%CI:3.82~12.75)、5.1个月(95%CI:3.14~12.26),组间比较差异有统计学意义(χ^(2)=4.21,P=0.040)。观察组和对照组中位总生存时间分别为12.9个月(95%CI:6.25~15.46)、9.7个月(95%CI:4.74~13.02),组间比较差异有统计学意义(χ^(2)=4.43,P=0.035)。结论深部热疗联合信迪利单抗及nab-PC方案治疗驱动基因阴性、PD-L1表达阳性的晚期鳞状NSCLC,能有效降低患者血清肿瘤标志物水平及免疫组织化学标志物阳性表达率,提高患者生命质量,提高疗效。

Objective To investigate the clinical efficacy and safety of deep hyperthermia combined with sintilimab and nab-PC(albumin-bound paclitaxel+carboplatin)regimen in the treatment of advanced squamous non-small cell lung cancer(NSCLC)with driver gene negative and programmed death-1 receptor ligand 1(PD-L1)expression positive.Methods A prospective case-control study was performed.A total of 84 advanced squamous NSCLC patients with driver gene negative and PD-L1 expression positive in Hebei Seventh People's Hospital from January 2020 to December 2022 were collected,and all patients were divided into the observation group and the control group according to the random number table method,with 42 cases in each group.The control group was given the treatment of sintilimab combined with nab-PC regimen,and the observation group was given deep hyperthermia on the basis of the control group.After 4 consecutive cycles of treatment,the short-term efficacy of the two groups was compared.The levels of serum tumor markers[carcinoembryonic antigen(CEA),squamous cell carcinoma antigen(SCCA),cytokeratin fragment 19(CYFR21-1)],and the positive expression rates of immunohistochemistry markers[p40,p63,and cytokeratin 5/6(CK5/6)]before and after treatment were compared between two groups.Functional Assessment of Cancer Therapy-Lung cancer module(FACT-L)scores,the adverse reactions and the long-term survival of the two groups were compared.Results There were 26 males and 16 females in the observation group,and the age was(59±11)years;there were 22 males and 15 females in the control group,and the age was(58±11)years.The objective remission rate and the disease control rate were 71.43%(30/42),90.48%(38/42),respectively in the observation group,and 50.00%(21/42),80.95%(34/42),respectively in the control group;the objective remission rate in the observation group was higher than that in the control group,and the difference was statistically significant(χ^(2)=4.04,P=0.044);and there was no statistically significant difference in the disease control rate of both groups(χ^(2)=1.56,P=0.212).The levels of serum CEA,SCCA and CYFRA21-1,and the positive expression rates of p40,p63,and CK5/6 in the two groups after treatment were lower than those before treatment(all P<0.05);and the scores of physiological status,functional status,additional concern in FACT-L scores and the total score of the scale after treatment were higher than those before treatment(all P<0.05).There were no statistically significant differences in the incidence of adverse reactions including thrombocytopenia,neutropenia,leukopenia,anemia,fever of the two groups(all P>0.05).The median progression-free survival(PFS)time was 6.5 months(95%CI:3.82-12.75),5.1 months(95%CI:3.14-12.26),respectively in the observation group and the control group,and the difference in the median PFS time was statistically significantly of both groups(χ^(2)=4.21,P=0.040).The median overall survival(OS)time was 12.9 months(95%CI:6.25-15.46),9.7 months(95%CI:4.74-13.02),respectively in the observation group and the control group,and the difference in the median OS time was statistically significantly of both groups(χ^(2)=4.43,P=0.035).Conclusions Deep hyperthermia combined with sintilimab and nab-PC regimen in the treatment of advanced squamous NSCLC with driver gene negative and PD-L1 expression positive can effectively reduce the serum tumor markers levels and positive expression rate of immunohistochemical markers,improve the quality of life of patients,and increase the short-term and long-term efficacy.