Table 2.
Univariate and multivariate Cox regression analyses of cfDNA levels, CTC counts and clinical parameters. ECOG, Eastern Cooperative Oncology Group Performance Score. 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.
| Variable | Univariate | Multivariate | ||
|---|---|---|---|---|
| P‐value | Hazard ratio (95% CI) | P‐value | Hazard ratio (95% CI) | |
| PFS | ||||
| Baseline log cfDNA (high vs. low cfDNA, n = 50) | 0.009 | 2.89 (1.30–6.45) | 0.80 | 1.18 (0.28–5.01) |
| Baseline CTC count, CellSearch (≥ 1 vs. 0, n = 30) | 0.04 | 2.97 (1.04–8.45) | 0.006 | 9.36 (1.88–46.6) |
| ECOG (≥ 1 vs. 0, n = 50) | 0.20 | 2.09 (0.72–6.08) | 0.70 | 1.40 (0.24–8.15) |
| PD‐L1 expression in the tissue (≥ 80 vs. < 80, n = 50) | 0.40 | 0.68 (0.27–1.76) | 0.13 | 0.37 (0.10–1.36) |
| Sex (male vs. female, n = 50) | 0.40 | 0.71 (0.32–1.57) | 0.04 | 0.23 (0.05–0.97) |
| Age (years, n = 50) | 0.60 | 0.99 (0.93–1.04) | 0.30 | 1.05 (0.96–1.16) |
| Number of metastasis (> 2 vs. ≤ 2, n = 50) | 0.04 | 2.39 (1.03–5.55) | 0.006 | 9.21 (1.87–45.3) |
| Smoking (yes vs. no, n = 50) | 0.40 | 0.68 (0.25–1.82) | 0.03 | 11.4 (1.25–104) |
| Combined changes in CTC and cfDNA levels a | ||||
| Group 1 (CTCs < 1 and a low cfDNA level, n = 12) | – | Reference | – | – |
| Group 2 (CTCs < 1 and a high cfDNA level or CTCs ≥ 1 and a low cfDNA level, n = 10) | 0.005 | 5.37 (1.66–17.4) | 0.009 | 13.1 (1.91–90.1) |
| Group 3 (CTCs ≥ 1 and a high cfDNA level, n = 8) | 0.05 | 4.12 (0.98–17.4) | 0.01 | 14.5 (1.76–119) |
| Combined changes in CTC and cfDNA levels a | ||||
| Group A (CTCs < 1 and a low cfDNA level, n = 12) | – | Reference | – | – |
| Group B (CTCs < 1 and a high cfDNA level or CTCs ≥ 1 and a low cfDNA level or CTCs ≥ 1 and a high cfDNA level, n = 18) | 0.006 | 4.99 (1.60–15.6) | 0.005 | 13.6 (2.17–85.3) |
| OS | ||||
| Baseline log cfDNA (high vs. low cfDNA levels, n = 50) | 0.005 | 3.26 (1.43–7.47) | 0.90 | 1.13 (0.29–4.46) |
| Baseline CTC count, CellSearch (≥ 1 vs. 0, n = 30) | 0.03 | 2.71 (1.11–6.64) | 0.01 | 5.41(1.42–20.6) |
| ECOG (≥ 1 vs. 0, n = 42) | 0.06 | 4.05 (0.95–17.2) | 0.70 | 1.51 (0.25–8.99) |
| PD‐L1 expression in the tissue (≥ 80 vs. < 80, n = 50) | 0.50 | 1.36 (0.60–3.10) | 0.50 | 0.64 (0.20–2.04) |
| Sex (male vs. female, n = 42) | 0.70 | 1.18 (0.49–2.86) | 0.20 | 0.42 (0.10–1.76) |
| Age (years, n = 42) | 0.80 | 1.01 (0.95–1.07) | 0.20 | 1.07 (0.98–1.17) |
| Number of metastasis (>2 vs. ≤2, n = 42) | 0.005 | 3.12 (1.41–6.87) | 0.001 | 9.08 (2.35–35.1) |
| Smoking (yes vs. no, n = 42) | 0.60 | 0.77 (0.29–2.05) | 0.02 | 20.5 (1.54–273) |
| Combined changes in CTC and cfDNA levels a | ||||
| Group 1 (CTCs < 1 and a low cfDNA level, n = 12) | – | Reference | ||
| Group 2 (CTCs < 1 and a high cfDNA level or CTCs ≥ 1 and a low cfDNA, n = 10) | 0.14 | 2.33 (0.76–7.15) | 0.50 | 1.90 (0.33–11.0) |
| Group 3 (CTCs ≥ 1 and a high cfDNA level, n = 8) | 0.02 | 4.24 (1.29–14.0) | 0.01 | 6.39 (1.37–29.8) |
| Combined changes in CTC and cfDNA levels a | ||||
| Group A (CTCs < 1 and a low cfDNA level, n = 12) | – | Reference | – | – |
| Group B (CTCs < 1 and a high cfDNA level or CTCs ≥ 1 and a low cfDNA level or CTCs ≥ 1 and a high cfDNA level, n = 18) | 0.04 | 2.91 (1.05–8.07) | 0.05 | 4.02 (0.97–16.6) |
a
Multivariate Cox regression model including sex, age, Eastern Cooperative Oncology Group Performance Score, PD‐L1 expression in the tissue, number of metastases and smoking status.