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