Abstract:Objective To explore the clinical efficacy of microwave thermal ablation combined with gemcitabine and cisplatin（GP）regimen in the treatment of non-small cell lung cancer（NSCLC）and its influence on the levels of circulating tumor DNA（ctDNA）and serum exosome markers. Methods A total of 82 NSCLC patients admitted to Cangzhou People’s Hospital from January 2022 to December 2024 were retrospectively enrolled and divided into two groups according to the treatment regimen：the control group（41 cases）was treated with GP regimen alone，while the study group（41 cases）was treated with microwave ablation on the basis of GP regimen. The clinical efficacy，levels of ctDNA，circulating tumor cells（CTCs），serum exosome markers［programmed deathligand 1（PD-L1），microRNA（miR）- 21，miR - 330］，tumor markers［neuron - specific enolase（NSE），carbohydrate antigen 125（CA125）， cytokeratin 19 fragment（CYFRA21-1）］before and after treatment，and the incidence of adverse reactions during treatment were compared between the two groups. Results The disease control rate of the study group was higher than that of the control group（95.12% vs 78.05% ，χ2=5.145，P=0.023）. After treatment，the levels of ctDNA，CTCs，CYFRA21-1，CA125 and NSE in both groups decreased，and those in the study group were lower than those in the control group（P<0.05）. The levels of exosomal PD-L1 and miR-21 in both groups decreased，while the level of miR-330 increased，and the improvement degree of each index in the study group was better than that in the control group（P<0.05）. The incidence of adverse reactions in the study group was lower than that in the control group（12.20% vs 36.59%，χ2=6.613，P=0.010）. Conclusion Microwave thermal ablation combined with GP regimen in the treatment of NSCLC can improve clinical efficacy，reduce the levels of ctDNA，CTCs，exosomal PD-L1 and miR-21，increase the level of miR-330，decrease the levels of tumor markers，and reduce adverse reactions.