Background
Methods
Study approval
Patients and blood sample collection
CEC enumeration
Antibody suspension bead array system
Statistical analyses
Results
Patient characteristics
Mean CEC level 166 cells/4 mL | Range (2–1195 cells/4 mL) | Total |
P
a
| ||
---|---|---|---|---|---|
≥ 166 cells/4 mL | <166 cells/4 mL | ||||
CEChigh
| CEClow
| ||||
12 | 25 | 37 | |||
Age | Over 70 | 8 | 10 | 18 (49%) | 0.17 |
Below 70 | 4 | 15 | 19 (51%) | ||
Sex | Male | 7 | 17 | 24 (65%) | 0.72 |
Female | 5 | 8 | 13 (35%) | ||
Stage | III | 3 | 11 | 14 (38%) | 0.59 |
IV | 8 | 12 | 20 (54%) | ||
Recurrence | 1 | 2 | 3 (8%) | ||
ECOG PS | 0 | 5 | 18 | 23 (62%) | 0.09 |
1 | 6 | 4 | 10 (27%) | ||
2 | 1 | 3 | 4 (11%) | ||
Pancreatic tumor location | Head | 5 | 12 | 17 (46%) | >0.9 |
Body | 5 | 9 | 14 (38%) | ||
Tail | 2 | 4 | 6 (16%) | ||
CA19-9 (U/mL) | ≥10,000 | 3 | 5 | 8 (22%) | >0.9 |
< 10,000 | 9 | 20 | 29 (78%) | ||
CRP (mg/dL) | ≥1.0 | 7 | 3 | 10 (27%) | <0.01 |
<1.0 | 5 | 22 | 27 (73%) | ||
Histology | Poorly differentiated | 5 | 9 | 14 (38%) | 0.62 |
Moderately differentiated | 4 | 10 | 14 (38%) | ||
Adenosquamous | 1 | 0 | 1 (2%) | ||
N.E (cytology only) | 2 | 6 | 8 (22%) | ||
Tumor response | Partial response | 2 | 2 | 4 (11%) | <0.05 |
Stable disease | 4 | 18 | 22 (59%) | ||
Progressive disease | 6 | 5 | 11 (30%) | ||
Second line therapy | S-1 | 6 | 12 | 18 (49%) | 1 |
Oxaliplatin + S-1 | 0 | 2 | 2 (5%) | ||
No | 6 | 11 | 17 (46%) |
Baseline levels of CECs and angiogenic factors
Univariate analysis | HR | 95% CI |
P
|
---|---|---|---|
Age: Over 70 vs. Below 70 | 0.52 | 0.25–1.13 | 0.1 |
Sex: Male vs. Female | 1.00 | 0.48–2.08 | 0.99 |
Stage: IV + Recurrence vs. III | 2.21 | 1.03–4.71 | 0.04 |
ECOG PS: 2 + 1 vs. 0 | 2.72 | 1.29–5.70 | 0.008 |
Pancreatic tumor location: Head vs. Others | 0.94 | 0.46–1.90 | 0.86 |
CA19-9 (cut-off: 10,000 U/mL): CA19-9high vs. CA19-9low
| 1.77 | 0.75–4.15 | 0.19 |
CRP level (cut-off: 1.0 mg/dL): CRPhigh vs. CRPlow
| 2.49 | 1.14–5.42 | 0.02 |
Histology: Poorly differentiated vs. Others | 1.09 | 0.52–2.27 | 0.82 |
Second line therapy: Yes vs. No | 0.61 | 0.30–1.24 | 0.17 |
CEC level (cut-off: 166 cells/4 mL): CEChigh vs. CEClow
| 5.18 | 2.23–12.03 | <0.001 |
IL-6 (cut-off: 19.3 pg/mL): IL-6high vs. IL-6low
| 2.52 | 0.73–8.64 | 0.14 |
IL-8 (cut-off: 11.3 pg/mL): IL-8high vs. IL-8low
| 1.74 | 0.82–3.67 | 0.15 |
IL-10 (cut-off: 7.82 pg/mL): IL-10high vs. IL-10low
| 5.05 | 1.55–16.39 | 0.007 |
VEGF (cut-off: 44.1 pg/mL): VEGFhigh vs. VEGFlow
| 1.22 | 0.60–2.47 | 0.59 |
PDGF-BB (cut-off: 1127.5 pg/mL): PDGF-BBhigh vs. PDGF-BBlow
| 0.93 | 0.43–2.04 | 0.86 |
HGF (cut-off: 471.3 pg/mL): HGFhigh vs. HGFlow
| 2.52 | 1.22–5.21 | 0.01 |
SDF-1 alpha (cut-off: 110.6 pg/mL): SDF-1 alphahigh vs. SDF-1 alphalow
| 1.23 | 0.60–2.53 | 0.56 |
Multivariate analysis
|
HR
|
95% CI
|
P
|
Stage: IV + Recurrence vs. III | 2.04 | 0.78–5.35 | 0.15 |
ECOG PS: 2 + 1 vs. 0 | 2.58 | 0.98–6.76 | >0.05 |
CRP level (cut-off: 1.0 mg/dL): CRPhigh vs. CRPlow
| 2.04 | 0.62–6.76 | 0.24 |
CEC level (cut-off: 166 cells/4 mL): CEChigh vs. CEClow
| 5.14 | 1.83–14.45 | 0.002 |
IL-10 (cut-off: 7.82 pg/mL): IL-10high vs. IL-10low
| 5.26 | 1.26–22.22 | 0.02 |
HGF (cut-off: 471.3 pg/mL): HGFhigh vs. HGFlow
| 1.34 | 0.46–3.91 | 0.59 |
Changes in CEC number during treatment
Association between CEC number and blood angiogenic factors
Mean ± SD | Spearman’s rank correlation coefficient |
P
| |
---|---|---|---|
CEC (cells/4 mL) | 166.2 ± 228.9 | 1 | - |
IL-6 (pg/mL) | 19.3 ± 52.4 | 0.17 | 0.30 |
IL-8 (pg/mL) | 11.3 ± 10.1 | 0.38 | 0.02 |
IL-10 (pg/mL) | 7.82 ± 26.9 | 0.45 | 0.006 |
VEGF (pg/mL) | 44.1 ± 38.8 | 0.34 | 0.04 |
PDGF-BB (pg/mL) | 1,127.5 ± 941.5 | 0.24 | 0.16 |
HGF (pg/mL) | 471.3 ± 249.0 | 0.37 | 0.02 |
SDF-1alpha (pg/mL) | 110.6 ± 43.7 | 0.15 | 0.37 |
CRP (mg/dL) | 1.9 ± 3.9 | 0.31 | 0.06 |
CA19-9 (U/mL) | 18,229.1 ± 55,377.8 | 0.11 | 0.50 |
CEA (ng/mL) | 18.3 ± 51.0 | 0.03 | 0.88 |