Consecutively resected NSCLCs were evaluated for
cfDNA levels in preoperative plasma (PLS1), intraoperative pleural-lavage (PLV) and postoperative (at 1 month) plasma sample (PLS2).
CfDNA was isolated and measured quantitatively by qPCR in a TaqMan probe-detection approach using the human β-actin gene as the amplifying target.
RESULTS: All (n = 34) except one were negative for malignant cells in PLV cytology.
CfDNA could be isolated from all the three samples (PLS1, PLV, and PLS2) successfully in each patient. The median
cfDNA levels in PLS1, PLV and PLS2 were 118 ng/mL (IQR 61-158), 167 ng/mL (IQR 59.9-179.9) and 103 ng/mL (IQR 66.5-125.4) respectively. The median follow-up was 34.1 months (IQR 25.2-41.6). A significant overall-survival (OS) and disease-free survival (DFS) were recorded for patients with
cfDNA level cut-offs
at 125, 170, and 100 ng/mL, respectively for PLS1, PLV, and PLS2. Patients with raised
cfDNA in PLS1 (>125 ng/mL) and PLV (>170 ng/mL) had significantly poorer 2-year OS, p = 0.005 and p = 0.012, respectively. The hazards (OS) were also higher for those with raised
cfDNA in PLV (HR = 5.779, 95% CI = 1.162-28.745, p = 0.032). PLV (>170 ng/mL) had increased pleural recurrences (p = 0.021) and correlated significantly with poorer DFS at 2-years (p = 0.001) with increased hazards (HR = 9.767, 95% CI = 2.098-45.451, p = 0.004). Multivariable analysis suggested higher
cfDNA in PLV as a poor prognostic factor for both OS and DFS.
CONCLUSIONS: Among patients with operable NSCLC, it is feasible to identify
cfDNA in pleural lavage and correlate PLV
cfDNA with pleural recurrences and outcomes.