Table 1.
Univariable Cox proportional hazards regression analysis.
| Variable | Cut-Off | PFS Risk | OS Risk | |||
|---|---|---|---|---|---|---|
| HR (95% CI) | p-Value | HR (95% CI) | p-Value | |||
| Prior adjuvant therapy | 0.7 (0.4–1.0) | 0.043 | 0.7 (0.4–1.0) | 0.046 | ||
| Number of metastatic sites | 1.3 (1.2–1.5) | <0.001 | 1.3 (1.2–1.5) | < 0.001 | ||
| Primary tumor in situ | 1.5 (1.1–2.0) | 0.013 | 1.8 (1.3–2.4) | < 0.001 | ||
| Presence of KRAS mutation | 1.0 (0.7–1.3) | 0.839 | 1.1 (0.8–1.5) | 0.666 | ||
| Presence of BRAF mutation | 3.0 (2.0–4.6) | <0.001 | 2.7 (1.8–4.0) | < 0.001 | ||
| Presence of NRAS mutation | 1.19 (0.60–2.40) | 0.629 | 1.0 (0.5–2.0) | 1.000 | ||
| Right-sidedness of primary tumor (transverse colon, hepatic flexure, ascending colon, cecum) | 1.3 (1.0–1.8) | 0.042 | 1.6 (1.2–2.1) | 0.001 | ||
| Treatment arm | 1.1 (0.9–1.4) | 0.465 | 1.2 (0.9–1.5) | 0.313 | ||
| ECOG performance status | 1.4 (1.1–1.8) | 0.012 | 1.4 (1.1–1.9) | 0.006 | ||
| age | 1.0 (1.0–1.0) | 0.078 | 1.0 (1.0–1.0) | 0.290 | ||
| gender | 1.0 (0.7–1.3) | 0.958 | 1.0 (0.7–1.3) | 0.773 | ||
| CellSearch Populations | ||||||
| CTCs (log transformed) | - | 1.2 (1.1–1.4) | 0.004 | 1.6 (1.4–1.9) | <0.001 | |
| ≥ 3 CTCs | 3 | 1.4 (1.1–1.9) | 0.012 | 2.2 (1.7–3.0) | <0.001 | |
| tdEVs (log-transformed) | - | 1.8 (1.4–2.3) | <0.001 | 2.5 (2.0–3.2) | <0.001 | |
| ≥ 40 tdEVs | 40 | 2.0 (1.5–2.6) | <0.001 | 2.7 (2.0–3.5) | <0.001 | |
| CECs (log-transformed) | - | 1.1 (0.9–1.5) | 0.338 | 1.0 (0.8–1.2) | 0.767 | |
| ≥ 66 CECs | 66 | 0.9 (0.7–1.3) | 0.703 | 0.7 (0.5–1.0) | 0.051 | |
| edEVs (log-transformed) | - | 1.7 (1.2–2.5) | 0.004 | 1.9 (1.3–2.8) | 0.002 | |
| ≥ 287 edEVs | 287 | 1.8 (1.3–2.5) | <0.001 | 2.1 (1.5–2.8) | <0.001 | |
| Other CellSearch Populations | ||||||
| Leukocytes a
(log-transformed) |
- | 1.3 (1.1–1.5) | 0.009 | 1.3 (1.1–1.6) | 0.001 | |
| ldEVs a
(log-transformed) |
- | 1.1 (0.9–1.4) | 0.437 | 1.2 (0.9–1.5) | 0.219 | |
| Nucleated a
(log-transformed) |
- | 1.1 (0.9–1.4) | 0.239 | 1.3 (1.0–1.6) | 0.048 | |
| Leukocytes b
(log-transformed) |
- | 1.1 (0.8–1.5) | 0.737 | 1.1 (0.8–1.5) | 0.751 | |
| ldEVs b
(log-transformed) |
- | 1.0 (0.7–1.4) | 0.976 | 1.1 (0.8–1.6) | 0.608 | |
| Nucleated b
(log-transformed) |
- | 1.1 (0.9–1.5) | 0.436 | 1.3 (1.0–1.7) | 0.091 | |
| CD105+ leukocytes b
(log-transformed) |
- | 1.0 (0.9–1.2) | 0.789 | 1.0 (0.8–1.2) | 0.927 | |
| CD105+ ldEVs b
(log-transformed) |
- | 1.0 (0.8–1.2) | 0.842 | 1.1 (0.9–1.4) | 0.203 | |
| CBC-Based Parameters | ||||||
| Leukocytes (log-transformed) |
- | 6.0 (2.1–16.9) | 0.001 | 9.5 (3.5–25.9) | <0.001 | |
| Platelets (log-transformed) |
- | 4.0 (1.6–10.3) | 0.004 | 5.3 (2.1–13.4) | <0.001 | |
| Hemoglobin, per 1 g/dL | - | 0.8 (0.7–0.9) | <0.001 | 0.7 (0.6–0.8) | <0.001 | |
| Alkaline phosphatase (ALP) (log-transformed) |
2.7 (1.6–4.4) | <0.001 | 3.8 (2.4–6.2) | <0.001 | ||
| Baseline serum lactate Dehydrogenase (LDH) (log-transformed) |
1.9 (1.3–2.8) | 0.002 | 2.4 (1.6–3.5) | <0.001 | ||
a Refers to populations co-isolated with the CTC kit; b refers to populations co-isolated with the circulating endothelial cell (CEC) kit.