Esophageal Cancer:
Precise Prediction
KSHIVETS OLEG, MD, PHD
SURGERY DEPARTMENT, ROSHAL HOSPITAL, ROSHAL,
MOSCOW, RUSSIA

ABSTRACT
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for esophageal cancer (EC) patients (ECP) (T1-
4N0-2M0) was analyzed.
METHODS: We analyzed data of 556 consecutive ECP (age=56.5±8.9 years; tumor size=6±3.5 cm) radically
operated (R0) and monitored in 1975-2022 (m=415, f=141; esophagogastrectomies (EG) Garlock=287, EG
Lewis=269, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea,
pericardium, splenectomy=167; adenocarcinoma=318, squamous=228, mix=10; T1=129, T2=115, T3=184, T4=128;
N0=281, N1=70, N2=205; G1=157, G2=141, G3=258; early EC=110, invasive=446; only surgery=424, adjuvant
chemoimmunoradiotherapy-AT=132: 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 1877±2221.6 days and cumulative 5-year survival (5YS) reached 52%, 10
years – 45%, 20 years – 33.4%, 30 years – 27%. 186 ECP lived more than 5 years (LS=4283.3±2412.6 days), 99
ECP – more than 10 years (LS=5883±2296.6 days). 227 ECP died because of EC (LS=631.8±323.4 days). AT
significantly improved 5YS (60.3% vs. 42%) (P=0.0029 by log-rank test). Cox modeling displayed that 5YS of ECP
significantly depended on: phase transition (PT) N0—N12 in terms of synergetics, cell ratio factors (ratio between
cancer cells- CC and blood cells subpopulations), T, G, histology, age, AT, localization, prothrombin index,
hemorrhage time, residual nitrogen, protein (P=0.000-0.021). Neural networks, genetic algorithm selection and
bootstrap simulation revealed relationships between 5YS and P PT early-invasive EC (rank=1); healthy cells/CC (2),
erythrocytes/CC (3), PT N0—N12 (4) thrombocytes/CC (5); segmented neutrophils/CC (6), stick neutrophils/CC (7),
lymphocytes/CC (8), monocytes/CC (9); leucocytes/CC (10); eosinophils/CC (11). Correct prediction of 5YS was
100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5-year survival 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; 11) surgery type. Optimal diagnosis and
treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced
thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and
adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for
ECP with unfavorable prognosis.

Data:
 Males…………………………………………………...415
 Females………..……………………………...............141
 Age=56.5±8.9 years
 Tumor Size=6±3.5 cm
 Only Surgery.……………………………………........424
 Adjuvant Chemoimmunoradiotherapy
 (5FU+thymalin/taktivin, 5-6 cycles+ Radiotherapy
 45-50Gy)………………………..................................132

Radical Procedures:
 Esophagogastrectomies Lewis (R0)…………………269
 Esophagogastrectomies Garlock (R0)………...........287
 Combined Esophagogastrectomies with Resection
 of Pancreas, Liver, Trachea, Lung, Aorta, Vena
 Cava Superior, Colon Transversum, Diaphragm,
Pericardium, Splenectomy (R0)……………...............167
 2-Field Lymphadenectomy…………………………….366
 3-Field Lymphadenectomy.………………………….…190

Staging:
 T1……129 N0..….281 G1…………157
 T2……115 N1….....70 G2…………141
 T3……184 N2…...205 G3…………258
 T4……128 M0…..556
 Adenocarcinoma…………………………….318
 Squamos Cell Carcinoma…………………..228
 Mix………………….....…………………...........10
 Early Cancer……………………………...…...110
 Invasive Cancer…………………………..…..446

Survival Rate:
 Alive……………………………………….....292 (52.5%)
 5-Year Survivors…………..……………….186 (33.5%)
 10-Year Survivors…………………………...99 (17.8%)
 Losses………………………………………..227 (40.8%)
 General Life Span=1877±2221.6 days
 For 5-Year Survivors=4283.3±2412.6 days
 For 10-Year Survivors=5883±2296.6 days
 For Losses=631.8±323.4 days
 Cumulative 5-Year Survival……………………..52%
 Cumulative 10-Year Survival…………………....45%
 Cumulative 20-Year Survival…………………....33.4%

General Esophageal Cancer Patients Survival after Complete
Esophagogastrectomies (Kaplan-Meier) (n=556):
Survival Function
5YS=52%; 10YS=45%; 20YS=33.4%.
Complete Censored
-5 0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomy
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving

Results of Univariate Analysis of Phase Transition Early—Invasive Cancer in
Prediction of Esophageal Cancer Patients Survival (n=556):
Cumulative Proportion Surviving (Kaplan-Meier)
5YS of Early ECP=100%; 5YS of Invasive ECP=39.2%;
P=0.0000 by Log-Rank Test.
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomy
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
Invasive ECP=446
Early ECP=110

Results of Univariate Analysis of Phase Transition N0—N1-2
in Prediction of Esophageal Cancer Patients Survival (n=556):
Cumulative Proportion Surviving (Kaplan-Meier)
5YS of ECP with N0=73.4%; 5YS of ECP with N12=29%;
P=0.0000 byLog-Rank Test.
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomy
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
ECP with N12
ECP with N0

Results of Univariate Analysis of Adjuvant Chemoimmunoradiotherapy
in Prediction of Esophageal Cancer Patients Survival (n=556):
Cumulative Proportion Surviving (Kaplan-Meier)
5YS of ECP after Adjuvant Chemoimmunoradiotherapy=68.4%;
5YS of ECP after Surgery along=48.6%;
P=0.0005 by Log-Rank Test.
Complete Censored
0 5 10 15 20 25 30
Years after Esophagogastrectomy
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
ECP after Adjuvant Chemoimmunoradiotherapy
ECP after Surgery along

Results of Univariate Analysis of Localization (Upper/3 vs. Others) in
Prediction of Esophageal Cancer Patients Survival (n=556):
Cumulative Proportion Surviving (Kaplan-Meier)
5YS of ECP in Upper/3=65%; 5YS of Others ECP=49.6%;
P=0.00297 by Log-Rank Test.
Complete Censored
0 5 10 15 20 25
Years after Esophagogastrectomy
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
Others
ECP with Upper/3

Results of Cox Regression Modeling in Prediction of Esophageal Cancer Patients
Survival after Complete Esophagogastrectomies (n=556):
Cox Regression, n=556
Parameter
Estimate
Standard
Error
Chi-square P value
Hazard
Ratio
Hemorrhage Time 0.00149 0.000397 14.05790 0.000177 1.00149
Residual Nitrogen 0.04793 0.010884 19.39363 0.000011 1.04910
Protein 0.02047 0.008585 5.68498 0.017111 1.02068
Prothrombin Index 0.02498 0.006343 15.50974 0.000082 1.02529
T1-4 0.42183 0.085559 24.30742 0.000001 1.52475
Phase Transition N0--N12 0.61686 0.160454 14.78006 0.000121 1.85311
Age 0.02866 0.007712 13.80670 0.000203 1.02907
Histology -0.28849 0.124708 5.35127 0.020707 0.74940
G1-3 0.42478 0.088723 22.92255 0.000002 1.52926
Adjuvant Treatment -0.86575 0.189974 20.76792 0.000005 0.42074
Segmented Neutrophils/Cancer Cells 3.68226 1.601024 5.28972 0.021452 39.73610
Localization -0.55622 0.190510 8.52432 0.003504 0.57337
Monocytes/Cancer Cells 3.96567 1.658738 5.71581 0.016813 52.75566
Lymphocytes/Cancer Cells 3.54668 1.621453 4.78447 0.028717 34.69776
Stick Neutrophils/Cancer Cells 3.97424 1.661423 5.72201 0.016754 53.20991
Leucocytes/Cancer Cells -3.74966 1.608956 5.43121 0.019780 0.02353
EEosinophils/Cancer Cells 3.89197 1.687090 5.32184 0.021060 49.00719

Results of Neural Networks Computing in Prediction of Esophageal Cancer
Patients Survival after Complete esophagogastrectomies (n=413):
Corect Classification Rate=100%
Error=0.000
Area under ROC Curve=1.000
Factors (n=413) Rank Sensitivity
Phase Transition Early---Invasive Cancer 1 24671
Healthy Cells/Cancer Cells
Erythrocytes/Cancer Cells
Phase Transition N0—N12
Thrombocytes/Cancer Cells
Segmented Neutrophils/Cancer Cells
Stick Neutrophils/Cancer Cells
Lymphocytes/Cancer Cells
Monocytes/Cancer Cells
Leucocytes/Cancer Cells
Eosinophils/Cancer Cells
2
3
4
5
6
7
8
9
10
11
23071
18425
18188
12766
7861
7164
6424
6229
5643
4982

Results of Bootstrap Simulation in Prediction of esophageal Cancer Patients Survival after
esophagogastrectomies (n=413):
Significant Factors (Number of Samples=3333) Rank Kendal Tau-A P
Tumor Size 1 -0.308 0.000
Healthy Cells/Cancer Cells 2 0.305 0.000
T1-4 3 -0.299 0.000
Erythrocytes/Cancer Cells 4 0.299 0.000
Leucocytes/Cancer Cells 5 0.290 0.000
Thrombocytes/Cancer Cells 6 0.285 0.000
Lymphocytes/Cancer Cells 7 0.281 0.000
Residual Nitrogen 8 -0.275 0.000
Segmented Neutrophils/Cancer Cells 9 0.273 0.000
Phase Transition N0---N12 10 -0.239 0.000
Hemorrhage Time 11 -0.228 0.000
Monocytes/Cancer Cells 12 0.227 0.000
Phase Transition Early---Invasive Cancer 13 -0.222 0.000
Esophageal/Cardioesophageal Cancer 14 -0.191 0.000
Operation Type 15 -0.187 0.000
Eosinophils/Cancer Cells 16 0.173 0.000
Stick Neutrophils/Cancer Cells 17 0.144 0.001
G1-3 18 -0.140 0.001
Tumor Growth 19 -0.113 0.01
Erythrocytes 20 0.100 0.01
Combined Procedure 21 0.095 0.01
Weight 22 0.092 0.01
Localization 23 0.069 0.05

Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of
Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=413):

Esophageal Cancer Dynamics:

Prognostic SEPATH-Model of Esophageal Cancer Patients Survival
after Complete Esophagogastrectomies (n=413):

5-year survival of ECP after radical
procedures significantly depended on:
1) PT “Early-Invasive Ccancer”;
2) PT N0--N12;
3) Cell Ratio Factors;
4) Blood Cell Circuit;
5) Biochemical Factors;
6) Hemostasis System;
7) Adjuvant Treatment;
8) EC Characteristics;
9) Tumor Localization;
10) Anthropometric Data;
11) Surgery Type.
CONCLUSION:

Address:
Oleg Kshivets, M.D.,Ph.D.
Consultant Thoracic, Abdominal,
General Surgeon & Surgical
Oncologist
 e-mail: okshivets@yahoo.com
 skype: okshivets
 http: //www.ctsnet.org/home/okshivets