叶酸受体阳性循环肿瘤细胞对可切除Ⅲ期鳞癌患者新辅助化疗联合免疫治疗后疗效的预测价值

doi:10.3969/j.issn.1006-7795.2024.04.015

首都医科大学学报 ›› 2024, Vol. 45 ›› Issue (4): 654-659.doi: 10.3969/j.issn.1006-7795.2024.04.015

• 肺癌新辅助免疫治疗临床研究 • 上一篇下一篇

叶酸受体阳性循环肿瘤细胞对可切除Ⅲ期鳞癌患者新辅助化疗联合免疫治疗后疗效的预测价值

刘洋, 杨磊, 韩毅^*

首都医科大学附属北京胸科医院胸外科，北京 101100

收稿日期:2024-04-22 出版日期:2024-08-21 发布日期:2024-07-08
通讯作者: 韩毅 E-mail:hanyeen@163.com
基金资助:
北京市属医学科研院所公益发展改革试点项目（JYY2023-14）。

The predictive value of folate receptor-positive circulating tumor cells in patients with resectable stage Ⅲ squamous cell carcinoma after neoadjuvant chemotherapy combined with immunotherapy

Liu Yang，Yang Lei，Han Yi^*

Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing 101100, China

Received:2024-04-22 Online:2024-08-21 Published:2024-07-08
Supported by:
This study was supported by Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes（JYY2023-14）.

摘要/Abstract

摘要： 目的研究治疗后叶酸受体阳性循环肿瘤细胞（folate receptor-positive circulating tumour cells,FR+-CTCs）对可切除Ⅲ期鳞癌患者新辅助化学药物治疗(以下简称化疗)联合免疫治疗疗效的预测价值。方法收集首都医科大学附属北京胸科医院2021年6月至2023年6月入院可切除Ⅲ期鳞癌患者，经过2周期新辅助化疗联合免疫治疗，记录患者以下指标：①一般临床资料：年龄、性别、临床分期、肿瘤位置、治疗前后白细胞计数；②治疗前后肿瘤标志物——血清癌胚抗原（carcinoembryonic antigen,CEA)、细胞角蛋白19片段（cytokeratin 19 fragment,CYFRA 21-1)、鳞状上皮细胞癌抗原（squamous cell carcinoma antigen，SCC）、FR+-CTCs数据；③患者术后病理结果，根据术后病理结果将患者分为两组，肿瘤病灶在病理层面上残存肿瘤细胞占比≤10%（缓解组，E组），肿瘤病灶在病理层面上残存肿瘤细胞占比>10%（NE组），比较E组和NE组患者的一般临床资料，治疗前后白细胞计数、肿瘤标志物和FR+-CTCs水平，将组间比较差异有统计学意义的变量纳入二元 Logistic 回归分析，统计分析出可切除Ⅲ期鳞癌患者新辅助化疗联合免疫治疗疗效的影响因素，采用受试者工作特征（receiver operating characteristics, ROC）曲线分析FR+-CTCs对其的预测价值。结果最终纳入24例患者，E组15例，NE组9例，两组患者一般临床资料、治疗前CEA、CYFRA 21-1、SCC、FR+-CTCs比较差异均无统计学意义（P >0.05），治疗后CEA、CYFRA 21-1、SCC差异无统计学意义（P >0.05），E组治疗后FR+-CTCs显著低于NE组（P<0.05），二元Logistic回归分析显示，治疗后FR+-CTCs（OR=1.28，95% CI： 1.00～1.63，P=0.047)是新辅助化疗联合免疫治疗的影响因素，ROC分析显示，治疗后FR+-CTCs截点值为10.10，特异度0.87，灵敏度0.89，曲线下面积（area under the curve，AUC）0.837。结论对可切除Ⅲ期鳞癌患者，治疗后FR+-CTCs低于10.10 FU/3 mL是预测新辅助化疗联合免疫治疗缓解效果的可靠指标。

关键词: 鳞癌, 叶酸受体阳性循环肿瘤细胞, 新辅助化疗联合免疫

Abstract: Objective To investigate the predictive value of folate receptor-positive circulating tumor cells (FR+-CTCs) in determining the efficacy of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable stage Ⅲ squamous cell carcinoma. Methods A total of patients diagnosed with resectable stage Ⅲ squamous cell carcinoma and admitted to Beijing Chest Hospital from June 2021 to June 2023 were included in this study. After receiving 2 cycles of neoadjuvant chemotherapy combined with immunotherapy, the following parameters were recorded: ① general clinical data including age, gender, clinical stage, tumor location，pre-and post-treatment white blood cell count; ② levels of tumor markers such as serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC), and FR+-CTCs before and after treatment; ③ postoperative pathological results, based on which the patients were divided into two groups: group E (<10% residual tumor cells) and NE group (>10% residual tumor cells). Binary Logistic regression analysis was performed using general clinical data, white blood cell count, tumor marker data, and FR+-CTCs data before and after treatment to statistically analyze factors influencing the efficacy of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable stage Ⅲ squamous cell carcinoma. The predictive value of FR+-CTCs was assessed using receiver operating characteristics (ROC) curve analysis. Results A total of 24 patients were included in this study, with 15 patients in group E and 9 patients in the NE group. There were no significant differences observed between the two groups regarding general clinical data or pre-treatment levels of CEA, CYFRA 21-1, SCC or FR+-CTCs(P >0.05). Additionally,no statistically significant differences were found for CEA,CYFRA21-1,and SCC levels after treatment.FR+-CTCs in group E was significantly lower than that in group NE (P<0.05). Binary Logistic regression analysis showed that FR+-CTCs after treatment (OR=1.28, 95%CI： 1.00-1.63, P=0.047) was the influencing factor of neoadjuvant chemotherapy combined with immunotherapy. ROC analysis showed that the cut-off value of FR+-CTCs after treatment was 10.10, with a specificity of 0.87, a sensitivity of 0.89, and an area under the curve of 0.837. Conclusion For patients with resectable Ⅲ squamous cell carcinoma, FR+-CTCs after treatment lower than 10.10 FU/3 mL can predict the remission effect of neoadjuvant chemotherapy combined with immunotherapy.

Key words: squamous cell carcinoma, folate receptor-positive circulating tumor cells, neoadjuvant chemotherapy combined with immunotherapy

中图分类号:

R734.2

刘洋, 杨磊, 韩毅. 叶酸受体阳性循环肿瘤细胞对可切除Ⅲ期鳞癌患者新辅助化疗联合免疫治疗后疗效的预测价值[J]. 首都医科大学学报, 2024, 45(4): 654-659.

Liu Yang, Yang Lei, Han Yi. The predictive value of folate receptor-positive circulating tumor cells in patients with resectable stage Ⅲ squamous cell carcinoma after neoadjuvant chemotherapy combined with immunotherapy[J]. Journal of Capital Medical University, 2024, 45(4): 654-659.

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叶酸受体阳性循环肿瘤细胞对可切除Ⅲ期鳞癌患者新辅助化疗联合免疫治疗后疗效的预测价值

The predictive value of folate receptor-positive circulating tumor cells in patients with resectable stage Ⅲ squamous cell carcinoma after neoadjuvant chemotherapy combined with immunotherapy

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