Abstract:

Objective

To analyze the predictive significance of circulating tumor DNA （ctDNA） in the risk of early recurrence of non-small cell lung cancer （NSCLC） after radical surgery.

Methods

All of 81 patients with NSCLC admitted to our hospital from February 2020 to December 2023 were selected. Radical resection was completed，tumor specimens and blood samples were collected. ctDNA analysis was performed using circulating single-molecule amplification and resequencing technology （cSMART） based on liquid biopsy.Relapse-free survival （RFS） and overall survival （OS） were recorded，and the relationship between ctDNA and RFS and OS was analyzed.

Results

81 cases had an average of （1.73±0.65） gene mutations，50 cases（61.73%） were positive ctDNA before surgery，and 33 of 76 cases （43.42%） were positive ctDNA at least one point after surgery. Among the 50 patients with positive ctDNA before surgery，26 patients had positive ctDNA after surgery. During a median follow-up of 44.0 months，Among the 81 NSCLC patients，55 survived（67.90%），37 cases （45.68%） relapsed and 26 cases （32.10%） died. The median RFS stage was 19.0 months （log rank=12.531，P＜0.001） and OS stage was 34.89 months （log rank=11.028，P =0.001） in ctDNA-positive patients before surgery，and the median RFS stage was 42.0 months and OS stage was 46.65 months in ctDNA-negative patients. Among the 33 ctDNA positive patients，21 casses （63.64%） relapsed and 15 cases（45.45%） died. The median RFS duration of 25.79 months （log rank=10.796，P =0.001） and OS duration of 34.21 months （log rank=7.384，P =0.007） in ctDNA-positive patients were shorter than those in ctDNA-negative patients （39.0 months of RFS and 43.15 months of OS）. The imaging results of 43 patients with negative ctDNA after surgery showed complete resection of the lesions，and 21 cases of them were positive ctDNA before surgery. The median RFS duration of those with negative ctDNA was 38.05 months （log rank=5.139，P =0.023），which was longer than that of those without negative ctDNA. 31 patients with negative ctDNA before surgery，7 cases（22.58%） had positive ctDNA conversion after surgery. Among the 33 ctDNA positive cases，21 cases had positive ctDNA after surgery （11.12±5.21） months earlier than the average results of imaging or clinical symptoms，and 17 cases had positive ctDNA within 2 weeks after surgery. Multifactor analysis showed that clinical stage and preoperative ctDNA status had statistical significance for RFS and OS（P＜0.05）. The risk of recurrence or death from high stage （stage Ⅲ） and low stage （stage Ⅰ/Ⅱ） NSCLC was 3.082 times or 3.577 times，respectively. Preoperative ctDNA-positive NSCLC had 3.889 times or 3.139 times increased risk of recurrence or death compared with ctDNA-negative NSCLC. Positive ctDNA was a factor affecting RFS after operation （P＜0.05），and the risk of recurrence was increased by 3.333 times.

Conclusion

Advanced stage and preoperative ctDNA positive are the factors affecting RFS and OS in patients with radical resection of NSCLC. The detection of ctDNA after surgery can help to detect recurrence in time.

Key words: Non-small cell lung cancer, Circulating tumor DNA, Minimal residual disease, Recurrence, Radical resection