Table 2.
Outcome predictors in 5-fluorouracil-treated patients with stage III colorectal cancer (Cox univariate analysis).
| Disease-Free Survival Institutional Cohort (n = 146) |
Disease-Specific Survival External Validation Set (n = 60) |
||||||
|---|---|---|---|---|---|---|---|
| No. of Recurrences (%) | HR (95% CI) | p | No. of Deaths (%) | HR (95% CI) | p | ||
| Densities of Tumor-Associated Macrophages (TAMs) and Neutrophils (TANs) | |||||||
| PT-TAMsa | low | 40/104 (38.5) | 1 (reference) | 0.002 | 22/49 (44.9) | 1 (reference) | 0.05 |
| high | 4/42 (9.5) | 0.20 (0.07–0.57) | 1/11 (9.1) | 0.14 (0.02–1.00) | |||
| LN-TAMsa | low | 32/68 (47.1) | 1 (reference) | 0.001 | NA | ||
| high | 3/39 (7.7) | 0.12 (0.04–0.41) | |||||
| PT-TANsb | low | 34/101 (33.7) | 1 (reference) | 0.04 | NA | ||
| high | 6/40 (15.0) | 0.41 (0.17–0.97) | |||||
| Patient Demographics | |||||||
| Age | ≥70 yrs. | 14 /35 (40.0) | 1 (reference) | 0.15 | 5/14 (35.7) | 1 (reference) | 0.47 |
| <70 yrs. | 30/111 (27.0) | 0.63 (0.33–1.18) | 18/46 (39.1) | 0.69 (0.25–1.88) | |||
| Gender | male | 27/91 (29.7) | 1 (reference) | 0.84 | 9/27 (33.3) | 1 (reference) | 0.38 |
| female | 17/55 (30.9) | 1.06 (0.58–1.95) | 14/33 (42.4) | 1.45 (0.63–3.36) | |||
| Tumor Pathology | |||||||
| Site | distal | 28/96 (29.2) | 1 (reference) | 0.59 | 17/41 (41.5) | 1 (reference) | 0.71 |
| proximal | 16/50 (32.0) | 1.18 (0.64–2.19) | 6/19 (31.6) | 0.83 (0.33–2.13) | |||
| Local Invasion | pT3 | 34/122 (27.9) | 1 (reference) | 0.13 | 17/47 (36.2) | 1 (reference) | 0.14 |
| pT4 | 10/24 (41.7) | 1.72 (0.85–3.49) | 6/13 (46.1) | 2.05 (0.80–5.31) | |||
| Nodal Invasion | N1 | 21/99 (15.1) | 1 (reference) | < 0.001 | 9/32 (28.1) | 1 (reference) | 0.03 |
| N2 | 23/47 (48.9) | 2.74 (1.52–4.96) | 14/28 (50.0) | 2.50 (1.08–5.80) | |||
| Grade | G1/G2 | 30/111 (27.0) | 1 (reference) | 0.13 | 13/38 (34.2) | 1 (reference) | 0.35 |
| G3 | 14/35 (40.0) | 1.62 (0.86–3.07) | 10/22 (45.4) | 1.48 (0.65–3.38) | |||
| Cell-Type | ADC | 38/127 (29.9) | 1 (reference) | 0.83 | 11/34 (32.3) | 1 (reference) | 0.77 |
| variants | 6/19 (31.6) | 1.10 (0.46–2.60) | 12/26 (46.1) | 0.88 (0.38–2.04) | |||
| Density of TILsc(quartiles) | 1st-to-3rd | 31/107 (26.4) | 1 (reference) | 0.51 | NA | ||
| 4th | 13/39 (27.8) | 1.24 (0.65–2.37) | |||||
| Vascular Invasion | no | 25/104 (24.0) | 1 (reference) | 0.008 | 16/50 (32.0) | 1 (reference) | 0.05 |
| yes | 19/42 (45.2) | 2.24 (1.23–4.08) | 7/10 (70.0) | 2.47 (1.01–6.01) | |||
| Tumor Molecular Features | |||||||
| MS Status | MSS | 41/129 (31.8) | 1 (reference) | 0.34 | 22/54 (40.7) | 1 (reference) | 0.19 |
| MSI | 41/129 (31.8) | 0.57 (0.18–1.84) | 1/6 (16.7) | 0.26 (0.04–1.97) | |||
| BRAF | wild-type | 41/139 (29.5) | 1 (reference) | 0.27 | 9/24 (37.5) | 1 (reference) | 0.77 |
| mutated | 3/7 (42.9) | 1.93 (0.60–6.24) | 2/3 (66.6) | 1.26 (0.27–5.96) | |||
| K-RAS | wild-type | 27/94 (28.7) | 1 (reference) | 0.89 | NA | ||
| mutated | 14/47 (29.8) | 1.05 (0.55–2.00) | |||||
NA, not available
a
percent CD68-immunoreactive area at the invasive front of primary tumors (PT-TAMs) or of metastatic lymph nodes (LN-TAMs, n = 107); low and high defined by an optimal cut-off of 8.0% for PT-TAMs and of 3.7% for LN-TAMs (see Receiver Operator Characteristic curve, Fig. 4)
b
percent CD66b-immune-reactive area in the intratumoral compartment (PT-TANs, n = 141); low and high defined by an optimal cut-off of 1.16 % (see Receiver Operator Characteristic curve, Fig. 4)
c
1st and 2nd quartiles not definable due to the absence of detectable immunoreactivity in 80 of 200 tested tissues