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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