Article Figures & Data
Figures
- Figure 1.
Flow chart and analysis plan of the study. Population selection during the study is summarized in the flow chart. In the left, the population selection during the study is described. In the right, the derived analysis and their synthetic results are summarized.
- Figure 2.
Distribution of Ang-2 measurement value among healthy volunteers (n = 41) and patients with mCRC (n = 109) involved in the final analysis. In our study population, the median value of Ang-2 was 4.045 ng/mL for the 109 patients included in the final analysis. In consequence, to investigate a cutoff value for clinical use, a level of 5 ng/mL seemed to be a relevant choice.
- Figure 3.
Kaplan–Meier curves for OS. A, the classic approach based on the GERCOR score in which LDH and PS are key parameters. B, the stratification according to the level of Ang-2. C, the stratification according to the level of Ang-2 in the 45 (41%) patients classified in intermediate risk with the GERCOR score. D, the determination of Ang-2 in the intermediate-risk patients with the GERCOR group (n = 45) reclassified these patients in two groups with similar profiles than low- and high-risk GERCOR groups.
Tables
- Table 1.
Baseline characteristics of patients, according to the cohort set
Overall population (N = 177) Cohort set-1 (N = 51) Cohort set-2 (N = 126) Characteristics N N N Pc Age, yd 51 126 ≤65 177 93 (53%) 27 (53%) 66 (52%) >65 84 (47%) 24 (47%) 60 (48%) 0.9461 Patient male sex, n (%)d 177 74 (42%) 51 28 (55%) 126 46 (37%) 0.0246 PS OMSd 167 0, n (%) 91 (55%) 48 27 (56%) 119 64 (54%) >0, n (%) 76 (45%) 21 (44%) 55 (46%) 0.7719 Primary tumor sited 177 51 126 Colon, n (%) 120 (68%) 32 (63%) 88 (70%) Rectum, n (%) 57 (32%) 19 (37%) 38 (30%) 0.3602 Metastases localizationd 177 51 126 Liver and other, n (%) 98 (55%) 17 (33%) 81 (64%) Liver alone, n (%) 68 (39%) 23 (45%) 45 (36%) Other alone, n (%) 11 (6%) 11 (22%) 0 (0%) 0.0001 Timing of metastasesd 173 48 125 Synchrone, n (%) 119 (69%) 30 (63%) 89 (71%) Metachrone, n (%) 54 (31%) 18 (37%) 36 (29%) 0.2688 Surgery of the primary tumor, n (%)d 175 110 (63%) 49 28 (57%) 126 82 (65%) 0.3293 Leucocyte (×106/mL)a 137 8.1 ± 3.2 49 8.1 ± 3.5 88 8.2 ± 3.0 0.8926 Lymphocyte (×106/mL)a 132 1.5 ± 0.7 45 1.7 ± 0.7 87 1.4 ± 0.6 0.0550 LDHd 115 33 82 ≤350 (ULN) 56 (49%) 20 (61%) 36 (44%) >350 (ULN) 59 (51%) 13 (39%) 46 (56%) 0.1050 Ang-2 (ng/mL)b 177 4.249 (2.683–7.153) 51 2.793 (2.103–4.330) 126 4.728 (3.298–7.798) 0.0001 Death eventd 177 51 36 (71%) 126 126 (100%) 0.0001 Median follow-up time in months 95% CI 57.9 (53.1–60.3) Max time observed = 64.1 All patients were follow-up until death NOTE: Bold characters represent significative results.
Abbreviation: ULN, upper limit of normal.
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↵aPlus–minus values are means ± SD, and the unpaired t test was used for the comparison of variable among groups.
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↵bMedian and interquartile range are described, and the Wilcoxon rank-sum test was used for the comparison of variable among groups.
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↵cP values are for the comparison between cohort set-1 and cohort set-2 populations.
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↵dχ2 or Fisher's exact tests were used for the comparison of categorical variables.
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- Table 2.
Univariate and multivariate analyses
Number of patients Number of deaths Univariate analysis Multivariate analysis Multivariate analysis with bootstrap procedure HR (95% CI) P HR (95% CI) P 95% percentile CI Age, y ≤65 93 84 1 (—) — >65 84 78 1.243 (0.912–1.694) 0.1689 Sex Male 74 65 1 Female 103 97 1.310 (0.955–1.798) 0.0941 PS OMS 0 91 80 1 >0 76 73 1.274 (0.927–1.751) 0.1355 Primary tumor site Colon 120 113 1 Rectum 57 49 0.855 (0.610–1.196) 0.3597 Timing to metastasis Metachronous 119 111 1 Synchronous 54 47 1.458 (1.035–2.054) 0.0308 Metastases localization Liver alone 68 59 1 Liver and other 98 95 1.816 (1.305–2.527) Other alone 11 8 0.686 (0.326–1.442) 0.0003 Surgery of the primary tumor Yes 110 101 1 No 65 59 1.433 (1.035–1.984) 0.0304 Leucocyte (×106/mL) 137 122 1.120 (1.056–1.188) 0.0002 Lymphocyte (×106/mL) 132 120 0.795 (0.589–1.073) 0.1339 LDH ≤350 (ULN) 56 49 1 1 >350 (ULN) 59 58 2.026 (1.373–2.988) 0.0004 1.598 (1.040–2.454) 0.0323 (1.039–2.628) Log_Ang-2 (pg/mL) 177 162 1.911 (1.492–2.448) <0.0001 1.587 (1.138–2.213) 0.0065 (1.161–2.263) NOTE: Bold characters represent significative results.
Abbreviation: ULN, upper limit of normal.
- Table 3.
Baseline characteristics of the patients involved in the multivariate analysis according to the Ang-2 level (n = 109)
Ang-2 < 5 ng/mL Ang-2 ≥ 5 ng/mL n (n = 69) (n = 40) Pb Age, yc ≤65 56 31 (45) 25 (63) >65 53 38 (55) 15(37) 0.11 Sexc Male 45 39 (57) 25 (63) Female 64 30 (43) 15 (37) 0.54 PS OMSc 0 57 41 (59) 16 (40) >0 52 28 (41) 24 (60) 0.07 Primary tumor sitec Colon 73 46 (67) 27 (68) Rectum 36 23 (33) 13 (32) 0.93 Timing to metastasisc Synchronous 74 39 (57) 35 (92) Metachronous 32 29 (43) 3 (8) <0.0001 Metastases localizationc Liver alone 43 28 (41) 15 (37) Liver and other 58 33 (48) 25 (63) Other alone 8 8 (12) 0 (0) 0.04515 Surgery of the primary tumorc No 73 16 (24) 18 (46) Yes 34 52 (76) 21 (54) 0.0189 Leucocyte (×106/mL)a 89 7.3713 ± 2.3972 9.4180 ± 3.8269 0.0026 Lymphocyte (×106/mL)a 85 1.6589 ± 0.6355 1.2187 ± 0.5816 0.0017 LDHc ≤350 (ULN) 52 43 (62) 9 (23) >350 (ULN) 57 26 (38) 31 (77) <0.0001 GERCOR scorec 0 Low-risk 32 29 (42) 3 (7) 1 Intermediate-risk 45 26 (38) 19 (48) 2 High-risk 32 14 (20) 18 (45) 0.0002 NOTE: Bold characters represent significative results.
Supplementary Data
Files in this Data Supplement:
- Supplementary Methods, Table 1 - Supplementary Methods, Table 1. Supplementary methods: - Ang-2 plasma sample measurement - Statistical analysis interpretation Supplementary table 1: - Cox Univariate analyses for OS prediction with and without the stratified approach (sensitivity analysis) Supplementary references
Volume 24, Issue 3
