Table 1 Patients’ characteristics
Factors
|
Training set (n = 162)
|
Validation set (n = 100)
|
Age, years (range)
|
65 (32–88)
|
65 (20–90)
|
Sex (female/male)
|
69 / 93
|
47 / 53
|
Tumor location (rectum/colon)
|
86 / 76
|
31 / 69
|
Surgical approach (open/lap)
|
154 / 8
|
8 / 92
|
Histological grade
(tub1/tub2/por, muc)
|
41 / 110 / 21
|
26 / 67 / 7
|
Lymphatic invasion (absent/present)
|
28 / 134
|
4 / 96
|
Vascular invasion (absent/present)
|
52 / 110
|
53 / 47
|
Tumor invasion (T1/T2/T3/T4)
|
11 / 16 / 90 / 45
|
8 / 16 / 65 / 11
|
Lymph node metastasis (N1/N2)
|
111 / 51
|
76 / 24
|
Stage (IIIA/IIIB/IIIC)
|
25 / 103 / 34
|
23 / 62 / 15
|
open = open surgery, lap = laparoscopic surgery, tub1 = well-differentiated adenocarcinoma, tub2: moderately differentiated adenocarcinoma, por = poorly differentiated adenocarcinoma, muc = mucinous adenocarcinoma
Table 2 Results of univariate and multivariate analyses of the disease-free survival in the training set
Factors
|
Univariate analysis
|
Multivariate analysis
|
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
Age (years) (≥66/<66)
|
1.081
|
0.602-1.939
|
0.795
|
|
|
|
Sex (female/male)
|
1.043
|
0.579-1.878
|
0.889
|
|
|
|
Tumor location (rectum/colon)
|
1.456
|
0.378-1.254
|
0.222
|
|
|
|
Surgical approach (open /lap)
|
1.160
|
0.209-3.561
|
0.838
|
|
|
|
Histological grade
(por, muc/tub1, tub2)
|
2.630
|
1.111-6.225
|
0.028*
|
1.295
|
0.482-3.478
|
0.608
|
Lymphatic invasion (present/absent)
|
1.132
|
0.394-1.978
|
0.761
|
|
|
|
Vascular invasion (present/absent)
|
1.808
|
0.895-3.652
|
0.099
|
|
|
|
Tumor invasion (T4/T1–3)
|
1.873
|
1.030-3.406
|
0.040*
|
1.342
|
0.681-2.644
|
0.396
|
Lymph node metastasis (N2/N1)
|
2.539
|
1.414-4.558
|
0.002*
|
2.765
|
1.447-5.284
|
0.002*
|
CRP, mg/dL (< 1.0/≥ 1.0)
|
3.110
|
1.387-6.976
|
0.006*
|
1.278
|
0.428-3.812
|
0.661
|
Alb, g/dL (< 3.5/≥ 3.5)
|
5.456
|
2.792-10.663
|
<0.001*
|
2.627
|
1.192-5.788
|
0.017*
|
Total lymphocyte counts
(<1600/≥1600)
|
1.430
|
0.792-2.584
|
0.236
|
|
|
|
Monocyte counts (≥450/<450)
|
2.887
|
1.532-5.438
|
0.001*
|
2.878
|
1.316-6.290
|
0.008*
|
Platelet counts (×103) (<165/≥165)
|
3.3793
|
1.666-6.853
|
0.003*
|
1.614
|
1.182-5.778
|
0.018*
|
HR = hazard ratio, CI = confidence interval, lap = laparoscopic surgery, open = open surgery, por = poorly differentiated adenocarcinoma, muc = mucinous adenocarcinoma, tub1 = well-differentiated adenocarcinoma, tub2 = moderately differentiated adenocarcinoma, CRP = C-reacted protein
Asterisk values indicate P-values < 0.05
Table 3 Results of univariate and multivariate analyses of the overall survival in the training set
Factors
|
Univariate analysis
|
Multivariate analysis
|
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
|
Age (years) (≥66/<66)
|
1.542
|
0.699-3.402
|
0.283
|
|
|
|
Sex (female/male)
|
1.210
|
0.552-2.653
|
0.634
|
|
|
|
Tumor location (rectum/colon)
|
1.560
|
0.704-3.455
|
0.273
|
|
|
|
Surgical approach (open /lap)
|
1.157
|
0.156-8.587
|
0.886
|
|
|
|
Histological grade
(por, muc/tub1–tub2)
|
1.949
|
0.571-6.644
|
0.286
|
|
|
|
Lymphatic invasion (present/absent)
|
0.888
|
0.303-2.603
|
0.828
|
|
|
|
Vascular invasion (present/absent)
|
2.116
|
0.793-5.648
|
0.135
|
|
|
|
Tumor invasion (T4/T1–3)
|
2.662
|
1.209-5.862
|
0.015*
|
1.812
|
0.749-4.385
|
0.181
|
Lymph node metastasis (N2/N1)
|
3.419
|
1.533-7.627
|
0.003*
|
4.959
|
2.009-12.291
|
<0.001*
|
CRP, mg/dL (< 1.0/≥ 1.0)
|
7.009
|
2.863-17.158
|
<0.001*
|
4.775
|
1.539-14.815
|
0.007*
|
Alb, g/dL (< 3.5/≥ 3.5)
|
12.540
|
5.197-30.264
|
<0.001*
|
4.489
|
1.620-12.439
|
0.004*
|
Total lymphocyte counts
(<1600/≥1600)
|
1.900
|
0.839-4.305
|
0.123
|
|
|
|
Monocyte counts (≥450/<450)
|
2.738
|
1.170-6.409
|
0.020*
|
2.564
|
0.868-7.577
|
0.089
|
Platelet counts (×103)(<165/≥165)
|
6.384
|
2.696-15.120
|
<0.001*
|
5.419
|
1.746-16.817
|
0.003*
|
HR = hazard ratio, CI = confidence interval, lap = laparoscopic surgery, open = open surgery, por = poorly differentiated adenocarcinoma, muc = mucinous adenocarcinoma, tub1 = well-differentiated adenocarcinoma, tub2 = moderately differentiated adenocarcinoma, CRP = C-reacted protein
Asterisk values indicate P-values < 0.05
Table 4 Results of univariate and multivariate analyses of the disease-free survival in the training set based on the KPS and TNM stage
Factors
|
Univariate analysis
|
Multivariate analysis
|
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
Age (years) (≥66/<66)
|
1.081
|
0.602-1.939
|
0.795
|
|
|
|
Sex (female/male)
|
1.043
|
0.579-1.878
|
0.889
|
|
|
|
Tumor location (rectum/colon)
|
1.456
|
0.378-1.254
|
0.222
|
|
|
|
Surgical approach (open /lap)
|
1.160
|
0.209-3.561
|
0.838
|
|
|
|
Histological grade
(por, muc/tub1, tub2)
|
2.630
|
1.111-6.225
|
0.028
|
1.663
|
0.670-4.128
|
0.273
|
Lymphatic invasion (present/absent)
|
1.132
|
0.394-1.978
|
0.761
|
|
|
|
Vascular invasion (present/absent)
|
1.808
|
0.895-3.652
|
0.099
|
|
|
|
CRP, mg/dL (< 1.0/≥ 1.0)
|
3.110
|
1.387-6.976
|
0.006
|
1.276
|
0.501-3.247
|
0.609
|
Total lymphocyte counts
(<1600/≥1600)
|
1.430
|
0.792-2.584
|
0.236
|
|
|
|
Adjuvant chemotherapy (absent/present)
|
1.679
|
0.892-3.158
|
0.108
|
|
|
|
Stage
|
|
|
|
|
|
|
(IIIB/IIIA)
|
3.262
|
0.766-13.887
|
0.110
|
2.108
|
0.624-7.117
|
0.230
|
(IIIC/IIIA)
|
6.456
|
1.454-28.661
|
0.014*
|
3.709
|
1.043-13.194
|
0.043*
|
(IIIC/IIIB)
|
2.081
|
1.048-4.134
|
0.036*
|
1.76
|
0.912-3.397
|
0.092
|
KPS
|
|
|
|
|
|
|
(1/0)
|
4.523
|
0.116-0.423
|
<0.001*
|
4.017
|
2.068-7.804
|
<0.001*
|
(≥2/0)
|
8.177
|
3.505-19.077
|
<0.001*
|
5.957
|
2.245-15.805
|
<0.001*
|
(≥2/1)
|
1.903
|
0.831-4.360
|
0.128
|
1.483
|
0.589-3.732
|
0.403
|
HR = hazard ratio, CI = confidence interval, lap = laparoscopic surgery, open = open surgery, por = poorly differentiated adenocarcinoma, muc = mucinous adenocarcinoma, tub1 = well-differentiated adenocarcinoma, tub2 = moderately differentiated adenocarcinoma, CRP = C-reacted protein, KPS = Kansai Prognostic Score
Asterisk values indicate P-values < 0.05
Table 5 Results of univariate and multivariate analyses of the overall survival in the training set based on the KPS and TNM stage
Factors
|
Univariate analysis
|
Multivariate analysis
|
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
Age (years) (≥66/<66)
|
1.542
|
0.699-3.402
|
0.283
|
|
|
|
Sex (female/male)
|
1.210
|
0.552-2.653
|
0.634
|
|
|
|
Tumor location (rectum/colon)
|
1.560
|
0.704-3.455
|
0.273
|
|
|
|
Surgical method (open /lap)
|
1.157
|
0.156-8.587
|
0.886
|
|
|
|
Histological grade
(por, muc/tub1, tub2)
|
1.949
|
0.571-6.644
|
0.286
|
|
|
|
Lymphatic invasion (present/absent)
|
0.888
|
0.303-2.603
|
0.828
|
|
|
|
Vascular invasion (present/absent)
|
2.116
|
0.793-5.648
|
0.135
|
|
|
|
CRP, mg/dL (< 1.0/≥ 1.0)
|
7.009
|
2.863-17.158
|
<0.001*
|
2.588
|
0.902-7.420
|
0.077
|
Total lymphocyte counts
(<1600/≥1600)
|
1.900
|
0.839-4.305
|
0.123
|
|
|
|
Adjuvant chemotherapy (absent/present)
|
2.295
|
1.010-5.216
|
0.047*
|
1.900
|
0.677-5.330
|
0.223
|
Stage
|
|
|
|
|
|
|
(IIIB/IIIA)
|
1.968
|
0.242-16.003
|
0.527
|
2.398
|
0.306-18.800
|
0.405
|
(IIIC/IIIA)
|
8.919
|
1.126-70.667
|
0.038*
|
6.015
|
0.748-48.347
|
0.092
|
(IIIC/IIIB)
|
3.821
|
1.472-9.915
|
0.006*
|
2.508
|
1.103-5.703
|
0.028*
|
KPS
|
|
|
|
|
|
|
(1/0)
|
5.575
|
2.105-14.767
|
<0.001*
|
4.588
|
1.674-12.574
|
0.003*
|
(≥2/0)
|
21.564
|
7.036-66.094
|
<0.001*
|
14.252
|
3.987-50.944
|
<0.001*
|
(≥2/1)
|
4.053
|
1.511-10.872
|
0.005*
|
3.106
|
1.037-9.305
|
0.043*
|
HR = hazard ratio, CI = confidence interval, lap = laparoscopic surgery, open = open surgery, por = poorly differentiated adenocarcinoma, muc = mucinous adenocarcinoma, tub1 = well-differentiated adenocarcinoma, tub2 = moderately differentiated adenocarcinoma, CRP = C-reacted protein, KPS = Kansai Prognostic Score
Asterisk values indicate P-values < 0.05
Table 6 C-indices of the TNM stage and the Kansai Prognostic score for the disease-free survival and overall survival
|
|
|
Prognostic score system
|
|
|
|
TNM stage
|
KPS (Alb, PC, MC)
|
C-index
|
Disease-free survival
|
TS
|
0.613*
|
0.707*
|
|
|
VS
|
0.586
|
0.618*
|
|
Overall survival
|
TS
|
0.660*
|
0.772*
|
|
|
VS
|
0.621*
|
0.708*
|
TNM stage = tumor-node-metastasis stage, KPS = Kansai Prognostic Score, Alb = albumin, PC = platelet counts, MC = monocyte counts, TS = training set, VS = validation set
Asterisk values indicate c-indices more than 0.600 (high)