Circulating tumor DNA mediates the effect of intrapleural cisplatin retention on non-small cell lung cancer malignant pleural effusion.

OBJECTIVES

To analyze the therapeutic effects of different cisplatin retention times on malignant pleural effusion and to explore whether circulating tumor DNA (ctDNA) played a mediating role in this process.

METHODS

A total of 207 patients with non-small cell lung cancer (NSCLC) and pleural effusion were enrolled. According to the retention time after intrapleural injection of cisplatin, patients were divided into three groups: a 1 h retention group (n=68), a 6 h retention group (n=69), and a 24 h retention group (n=70). The short-term efficacy (disease control rate, objective response rate) and long-term efficacy (progression-free survival, overall survival (OS)) were compared among the three groups, and the role of ctDNA was explored through mediation effect analysis.

RESULTS

The disease control rate in the 24 h retention group was 92.9%, significantly higher than that in the 6 h group (92.7%) and the 1 h group (80.9%) (P<0.05). Regarding survival outcomes, the median progression-free survival (PFS) in the 24 h group was 11.8 months, and the median OS was 18.5 months, both significantly longer than those in the 6 hr and 1 h groups (P<0.001). Mediation analysis showed that ctDNA concentration played a partial mediating role in the association between cisplatin retention duration and patient survival (both PFS and OS).

CONCLUSIONS

24 h intrapleural cisplatin retention significantly improves the short-term and long-term treatment outcomes in NSCLC patients with pleural effusion. Changes in ctDNA concentration play a key mediating role in this efficacy improvement, suggesting that ctDNA could serve as a novel potential biomarker for guiding personalized treatment.