Esophageal cancer patients’ survival after surgery significantly depended on cell ratio factors, blood cell circuit, biochemical factors, hemostasis system, adjuvant chemoimmunoradiotherapy, cancer characteristics, localization, anthropometric data

1. Esophageal cancer patients’ survival after surgery
significantly depended on cell ratio factors, blood cell circuit, biochemical
factors, hemostasis system, adjuvant chemoimmunoradiotherapy, cancer
characteristics, localization, anthropometric data
Kshivets Oleg Surgery Department, Roshal Hospital, Roshal, Moscow, Russia
OBJECTIVE: We examined factors in terms of precise prognosis of 5-year survival (5YS) of
esophageal cancer (EC) patients (ECP) (T1-4N0-2M0) after complete (R0)
esophagogastrectomies (EG).
METHODS: We analyzed data of 499 consecutive ECP (age=56.3±8.9 years; tumor
size=6.3±3.4 cm) radically operated and monitored in 1975-2017 (m=365, f=134;
esophagogastrectomies (EG) Garlock=280, EG Lewis=219, combined EG with resection of
pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium,
splenectomy=147; adenocarcinoma=284, squamous=205, mix=10; T1=92, T2=113,
T3=171, T4=123; N0=234, N1=69, N2=196; G1=140, G2=123, G3=236; early EC=73,
invasive=426; only surgery=382, adjuvant chemoimmunoradiotherapy-AT=117: 5-
FU+thymalin/taktivin+radiotherapy 45-50Gy). Multivariate Cox modeling, clustering,
SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine
any significant dependence.
RESULTS: Overall life span (LS) was 1763.2±2213.7 days and cumulative 5YS reached
47.3%, 10 years – 40.7%, 20 years – 29.8%. 148 ECP lived more than 5 years
(LS=4382.9±2551 days), 80 ECP – more than 10 years (LS=6027.2±2445.6 days). 223
ECP died because of EC (LS=630.2±320.5 days). AT significantly improved 5YS (67.7% vs.
43.1%) (P=0.00002 by log-rank test). Cox modeling displayed (Chi2=283.82, df=18,
P=0.0000) that 5YS of ECP significantly depended on: phase transition (PT) N0—N12 in
terms of synergetics, cell ratio factors (ratio between cancer cells and blood cells
subpopulations), T, G, age, AT, localization, blood cells, prothrombin index, coagulation
time, residual nitrogen (P=0.000-0.047). Neural networks, genetic algorithm selection and
bootstrap simulation revealed relationships between 5YS and PT N0--N12 (rank=1), PT
early-invasive EC (rank=2), T(3), AT(4), prothrombin index (5), glucose (6), healthy
cells/CC(7), thrombocytes/CC (8), erythrocytes/CC (9), segmented neutrophils/CC (10),
lymphocytes/CC (11), monocytes/CC (12) . Correct prediction of 5YS was 100% by neural
networks computing.
CONCLUSIONS: 5YS of ECP after radical procedures significantly depended on: 1) PT
“early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5)
biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor
localization; 10) anthropometric data.
Cox Regression:
Chi² = 283.823; df = 18; p = 0.0000
Chi-
square
P value 95%
Lower CL
95%
Upper CL
Hazard
Ratio
Segmented Neutrophils (%) 12.59441 0.000387 0.03158 0.109481 1.07308
Hemorrhage Time 15.84264 0.000069 0.00082 0.002423 1.00162
Rest Nitrogen 20.64268 0.000006 0.03104 0.078140 1.05611
Prothrombin Index 11.43536 0.000721 0.00966 0.036297 1.02324
Segmented Neutrophils (abs) 7.89311 0.004962 -0.51890 -0.092424 0.73664
Lymphocytes (abs) 9.84425 0.001704 0.32888 1.423661 2.40193
Phase Transition N0-N12 14.68809 0.000127 0.29536 0.913655 1.83035
Age 6.06829 0.013763 0.00388 0.034103 1.01917
G1-3 8.85519 0.002923 0.08452 0.410655 1.28093
Adjuvant Chemoimmunoradiotherapy 24.44581 0.000001 -1.43350 -0.619619 0.35824
Phase Transition Early-Invasive Cancer 0.44423 0.505088 -0.72846 1.479202 1.45553
Eosinophils (tot) 10.72787 0.001055 0.19683 0.783403 1.63251
Leucocytes/Cancer Cells 6.82931 0.008967 -5.02821 -0.718325 0.05651
Stick Neutrophils/Cancer Cells 10.17349 0.001425 1.39648 5.848322 37.42734
Segmented Neutrophils/Cancer Cells 5.89064 0.015222 0.52025 4.886223 14.92797
Lymphocytes/Cancer Cells 4.84886 0.027664 0.27517 4.731535 12.22342
Monocytes/Cancer Cells 13.24717 0.000273 2.04857 6.829331 84.68607
Localization 3.92404 0.047600 -0.76841 -0.004086 0.67960
Neural Networks :
Baseline Error=0.000
Area under ROC Curve=1.000
Correct Classification Rate=100%
Rank Sensitivity
Phase Transition N0-N12
Phase Transition Early-Invasive Cancer
T1-4
Adjuvant Chemoimmunoradiotherapy
Prothrombin Index
Glucose
Healthy Cells/Cancer Cells
Thrombocytes/Cancer Cells
Erythrocytes/Cancer Cells
Segmented Neutrophils/Cancer Cells
Lymphocytes/Cancer Cells
Monocytes/Cancer Cells
1
2
3
4
5
6
7
8
9
10
11
12
4301
3489
3181
2922
2258
1636
1530
1273
1008
443
427
351
Bootstap Simulation: Rank Kendall’Tau-A P<
Tumor Size
Healthy Cells/Cancer Cells
T1-4
Erythrocytes/Cancer Cells
Leucocytes/Cancer Cells
Thrombocytes/Cancer Cells
Lymphocytes/Cancer Cells
Segmented Neutrophils/Cancer Cells
Rest Nitrogen
Phase Transition N0-N12
Monocytes/Cancer Cells
Hemorrhage Time
Phase Transition Early-Invasive Cancer
Stick Neutrophils/Cancer Cells
Esophageal/Cardioesophageal Cancer
Chlorides
Eosinophils/Cancer Cells
G1-3
Tumor Growth
Histology
Erythrocytes (tot)
Glucose
Prothrombin Index
Localization
Weight
Stick Neutrophils (tot)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
-0.273
0.271
-0.268
0.263
0.250
0.249
0.243
0.231
-0.224
-0.214
0.209
-0.203
-0.172
0.161
-0.158
0.158
0.146
-0.120
0.119
-0.095
0.088
0.084
-0.084
0.078
0.078
0.068
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.001
0.01
0.05
0.05
0.05
0.05
0.05
0.05