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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

From: Prognostic impact of circulating tumor cell apoptosis and clusters in serial blood samples from patients with metastatic breast cancer in a prospective observational cohort

   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
  1. 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
  2. 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
  3. 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)
  4. 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
  5. d All four patients with clusters died before any of the patients in the group without clusters died (perfect prediction)
  6. e P-value from log-rank test