外周血循环肿瘤细胞在晚期肺鳞癌患者免疫联合化疗疗效及预后中的价值初探

Preliminary study on the value of peripheral blood circulating tumor cells in the efficacy and prognosis of immunotherapy combined with chemotherapy in patients with advanced lung squamous cell carcinoma

目的分析晚期肺鳞癌(LUSC)患者的循环肿瘤细胞(CTCs)计数及动态变化与临床病理特征、免疫联合化疗及安慰剂联合化疗治疗效果及预后的相关性。方法选取2018年10月~2020年2月扬州大学附属苏北人民医院诊治并接受CTCs检测的39例晚期LUSC患者为研究对象,分别于治疗前、治疗第2疗程后当天采集患者静脉血,采用免疫磁珠法和免疫荧光染色法检测CTCs数目,以CTCs=5个/6ml外周血作为非小细胞肺癌(NSCLC)CTCs的截断值。对39例晚期LUSC患者每2个疗程行影像学检查并评估临床疗效。分析CTCs数目与临床病理特征的关系、CTCs数目动态变化与免疫联合化疗及安慰剂联合化疗的疗效及预后的关系。结果基线CTCs数目与不同的患者年龄区间、性别、吸烟史、TNM分期、治疗前有无远处转移及ECOG评分差异无统计学意义(P>0.05),而与肿瘤最大直径的差异有统计学意义(P<0.05),且肿瘤直径越大,基线CTCs数值越大;治疗前后CTCs数目变化与卡瑞利珠单抗联合卡铂+紫杉醇疗效之间呈显著负相关(r=-0.533,P=0.041),而与安慰剂联合卡铂+紫杉醇疗效之间无相关性(r=0.258,P=0.223);采用Fisher精确检验评价RECIST和CTCs这两种疗效判定方法,差异无统计学意义(P>0.05);基线CTCs数目<5个/6ml外周血的患者较基线CTCs数目≥5个/6ml外周血的患者无进展生存期(PFS)更长(P=0.005)。治疗2个疗程后,CTCs数目<5/6ml外周血的患者和CTCs数目≥5个/6ml外周血的患者PFS差异有统计学意义(P=0.009);基线CTCs数目和治疗方式是患者PFS的独立影响因素(P<0.05);卡瑞利珠单抗联合卡铂+紫杉醇治疗的患者较安慰剂联合卡铂+紫杉醇治疗的患者PFS更长(P=0.001)。结论外周血CTCs检测对晚期LUSC患者免疫联合化疗及安慰剂联合化疗治疗效果和预后具有一定的预测价值。CTCs有望成为晚期LUSC临床疗效评价标准。

Objective To analyze the correlations of circulating tumor cells(CTCs)count and dynamic changes with clinicopathological characteristics,efficacy and prognosis of immunotherapy combined with chemotherapy and placebo combined with chemotherapy in patients with advanced lung squamous cell carcinoma(LUSC).Methods Thirty-nine patients with advanced LUSC who were diagnosed and treated in the Affiliated Subei People’s Hospital of Yangzhou University from Oct 2018 to Feb 2020 and were tested by CTCs.Venous blood was collected before treatment and on the day after the second course of treatment,and the number of CTCs was detected by immunomagnetic beads and immunofluorescence staining method.CTCs=5/6 ml peripheral blood was as NSCLC CTCs’cutoff value.Thirty-nine patients with advanced LUSC were examined by imaging every two courses and the clinical effects were evaluated.The relationship between the number of CTCs and clinicopathological characteristics,and the relationship between the dynamic changes of CTCs number and the efficacy and prognosis of immunotherapy combined with chemotherapy and placebo combined with chemotherapy were analyzed.Results There was no correlation between the number of baseline CTCs and patients with different age ranges,gender,smoking history,TNM staging,presence or absence of distant metastasis before treatment,and ECOG score(P>0.05),however,the CTC number was positively with the size of tumor diameter(P<0.05).And the larger the tumor diameter was,the greater the number of baseline CTCs was.The number of CTCs before and after treatment were significantly negatively correlated with the efficacy of carrelizumab combined with carboplatin+paclitaxel(r=-0.533,P=0.041),but there was no correlation with the efficacy of placebo combined with carboplatin+paclitaxel(r=0.258,P=0.223).Fisher’s exact test was used to evaluate the curative effects of RECIST and CTCs,and the difference was not statistically significant(P>0.05).The progression-free survival(PFS)of patients in the baseline CTCs<5/6 ml of peripheral blood was longer than that in the baseline CTCs≥5/6 ml of peripheral blood(P=0.005).After two courses of treatment,there was a statistical difference in PFS between patients with CTCs<5/6 ml and patients with CTCs≥5/6 ml(P=0.009).The number of baseline CTCs and different treatment were independent influencing factors for PFS(P<0.05).Patients treated with carrelizumab combined with carboplatin+paclitaxel had longer PFS than patients treated with placebo combined with carboplatin+paclitaxel(P=0.001).Conclusion Peripheral blood CTCs detection has a certain predictive value in the evaluation of the efficacy and prognosis of immunotherapy combined with chemotherapy and placebo combined with chemotherapy in advanced LUSC patients.CTCs detection is expected to be the standard of clinical efficacy evaluation.