Table 3.
Cox uni- and multivariable analysis by presence of apoptotic CTC, CTC clusters and WBC-CTC at base-line, 1–3 months, 6 months follow-up and by apoptotic CTC and clusters present at any time during the study (time-dependent covariates). At 1–3 and 6 months, CTC numbers categorized as ≥ 5 vs 0–4, is also presented
| PFS univariable | PFS multivariable | OS univariable | OS multivariable | ||||||||||
| BLa | (N = 52) | (N = 50)b | (N = 52) | (N = 50)b | |||||||||
| HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | ||
| Apoptosis | 1.3 | 0.60–2.7 | 0.52 | 1.1 | 0.34–3.5 | 0.88 | 1.5 | 0.60–3.8 | 0.38 | 3.0 | 0.73–12 | 0.13 | |
| Cluster | 0.90 | 0.37–2.2 | 0.81 | 0.83 | 0.21–3.4 | 0.80 | 1.1 | 0.36–3.1 | 0.92 | 0.73 | 0.11–4.9 | 0.75 | |
| WBC-CTC | 1.0 | 0.50–2.0 | 0.98 | 0.82 | 0.33–2.0 | 0.67 | 0.76 | 0.35–1.7 | 0.49 | 0.69 | 0.20–2.3 | 0.54 | |
| 1–3 months | (N = 45) | (N = 43)c | (N = 48) | (N = 46)c | |||||||||
| HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | ||
| ≥5 CTC | 4.6 | 2.0–11 | <0.001 | 4.3 | 1.1–17 | 0.041 | 5.8 | 2.3–14 | <0.001 | 34 | 3.1–367 | <0.001 | |
| Apoptosis | 4.9 | 2.1–11 | <0.001 | 4.5 | 1.0–20 | 0.047 | 5.7 | 2.4–14 | <0.001 | 10 | 1.2–87 | 0.031 | |
| Cluster | 7.4 | 2.3–24 | 0.001 | 2.0 | 0.30–14 | 0.46 | 9.8 | 2.5–38 | 0.001 | 3.1 | 0.48–20 | 0.23 | |
| WBC-CTC | 1.8 | 0.76–4.1 | 0.33 | 0.49 | 0.18–3.0 | 0.67 | 1.9 | 0.75–4.6 | 0.18 | 0.17 | 0.08–1.4 | 0.14 | |
| 6 months | (N = 32) | (N = 30)c | (N = 42) | (N = 35)c | |||||||||
| HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | ||
| ≥ 5 CTC | 6.1 | 2.1–17 | 0.001 | 53 | 4.5–613 | 0.002 | 2.7 | 1.0–7.1 | 0.047 | 0.47 | 0.02–13 | 0.66 | |
| Apoptosis | 4.8 | 1.7–13 | 0.003 | 2.1 | 0.34–13 | 0.42 | 6.2 | 2.2–18 | 0.001 | 79 | 5.5–1137 | 0.001 | |
| Cluster | 13 | 2.2–79 | 0.005 | 3.9 | 0.12–124 | 0.44 | +∞d | Undefined | <0.001e | Not included | |||
| WBC-CTC | 3.1 | 0.97–10 | 0.056 | 0.14 | 0.01–1.6 | 0.11 | 7.1 | 2.4–21 | <0.001 | 23 | 1.1–458 | 0.042 | |
| Time-dependent | (N = 52) | (N = 50)b | (N = 52) | (N = 50)b | |||||||||
| HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | HR | 95 % CI | P-value | ||
| Apoptosis | 5.0 | 2.2–11 | <0.001 | 6.7 | 2.4–19 | <0.001 | 6.4 | 2.6–16 | <0.001 | 25 | 5.2–115 | <0.001 | |
| Cluster | 4.8 | 1.9–12 | 0.001 | 1.8 | 0.51–6.5 | 0.36 | 16 | 4.6–58 | <0.001 | 7.0 | 1.7–28 | 0.006 | |
WBC-CTC white blood cells associated with CTC, PFS progression free survival, OS overall survival, HR Hazard ratio calculated with Cox Regression, CI confidence interval
a At BL, only patients with ≥5 CTCs were included and this variable (≥ 5 vs 0–4) is consequently not evaluated in survival analysis at this time point
b Adjusted for: CTC number ≥20, breast cancer subgroup, age at diagnosis (continuous), time to recurrence, number (≥3 vs 1–2) and site of metastases (categorical on 5 levels)
c Adjusted for: breast cancer subgroup, age at diagnosis, time to recurrence (continuous), number (≥3 vs 1–2) and site of metastases (categorical on 5 levels). Not adjusted for site of metastases at 6 months due to non-converging maximum likelihood estimation procedure
d All four patients with clusters died before any of the patients in the group without clusters died (perfect prediction)
e P-value from log-rank test