Table 2. Univariate and multivariate Cox regression analyses of cfDNA levels, CTC counts and clinical parameters.
| Variable | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| P value | HR (95% CI) | P value | HR (95% CI) | ||
| PFS | |||||
| Baseline log cfDNA (high vs. low cfDNA) | 0.001 | 5.06 (1.89–13.6) | 0.005 | 46.0 (3.16–672) | |
| Baseline CTC count, CellSearch (≥150 vs. <150) | 0.028 | 3.47 (1.14–10.6) | |||
| ECOG PS (≥2 vs. <2) | <0.001 | 3.57 (1.72–7.40) | 0.04 | 17.9 (1.11–289) | |
| Sex (male vs. female) | 0.2 | 1.76 (0.74–4.22) | |||
| Age (continue) | 0.5 | 1.01 (0.97–1.05) | |||
| Stage (IV vs. III) | 0.07 | 3.00 (0.91–9.91) | |||
| Number of metastasis (>2 vs. ≤2) | 0.1 | 1.70 (0.90–3.19) | |||
| Liver metastasis (yes vs. no) | 0.08 | 1.74 (0.93–3.23) | |||
| Smoking (smoker vs. former smoker) | 0.8 | 0.92 (0.49–1.70) | |||
| 3 weeks log cfDNA (high vs. low cfDNA)* | <0.0001 | 3.50 (1.69–7.23) | 0.004 | 3.49 (1.50–8.12) | |
| OS | |||||
| Baseline log cfDNA (high vs. low cfDNA) | 0.003 | 3.32 (1.50–7.37) | 0.004 | 32.4 (3.05–344) | |
| Baseline CTC count, CellSearch (≥150 vs. <150) | 0.07 | 2.71 (0.93–7.88) | |||
| ECOG PS (≥2 vs. <2) | <0.001 | 4.54 (2.13–9.68) | |||
| Sex (male vs. female) | 0.2 | 1.80 (0.75–4.36) | |||
| Age (continue) | 0.5 | 1.01 (0.97–1.06) | |||
| Stage (IV vs. III) | 0.08 | 2.86 (0.86–9.47) | |||
| Number of metastasis (>2 vs. ≤2) | 0.5 | 1.23 (0.65–2.33) | |||
| Liver metastasis (yes vs. no) | 0.3 | 1.45 (0.77–2.76) | |||
| Smoking (smoker vs. former smoker) | 0.5 | 0.82 (0.43–1.55) | |||
| 3 weeks log cfDNA (high vs. low cfDNA)* | <0.001 | 3.67 (1.72–7.82) | 0.002 | 4.35 (1.68–11.3) | |
| PD log cfDNA (high vs. low cfDNA)* | <0.001 | 5.73 (1.93–17.0) | 0.006 | 9.24 (1.87–45.6) | |
*, multivariate Cox regression model including sex, age, ECOG PS, stage, number of metastases, presence of liver metastasis and smoking status. The levels of cfDNA were determined as low (< cut-off) or high (≥ cut-off) based on the cut-off obtained from the ROC curve analyses. cfDNA, cell free DNA; CI, confidence interval; CTC, circulating tumor cell; ECOG PS, Eastern Cooperative Oncology Group Performance Score; PD, progression disease; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; ROC, receiver operating characteristics.