1.
Esophageal cancer cell dynamics significantly depended on
blood cell circuit, biochemical factors, hemostasis system,
cancer characteristics and anthropometric data
Kshivets Oleg
Surgery Department, Roshal Hospital, Roshal
Moscow, Russia
1433P

2.
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DECLARATION OF INTERESTS
Oleg Kshivets
No disclosures
Oleg Kshivets

3.
ESOPHAGEAL CANCER CELL DYNAMICS SIGNIFICANTLY DEPENDED ON BLOOD CELL CIRCUIT, BIOCHEMICAL
FACTORS, HEMOSTASIS SYSTEM, CANCER CHARACTERISTICS AND ANTHROPOMETRIC DATA #1433P
Oleg Kshivets, MD, PhD
Surgery Department, Roshal Hospital, Roshal, Moscow, Russia
OBJECTIVE: We examined factors significantly affecting esophageal cancer (EC) cell dynamics.
METHODS: We analyzed data of 553 consecutive EC patients (ECP) (age=56.5±8.9 years; tumor size=6±3.5 cm)
radically operated and monitored in 1975-2021 (m=413, f=140; esophagogastrectomies (EG) Garlock=286, EG Lewis=267,
combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium,
splenectomy=153; adenocarcinoma=316, squamous=227, mix=10; T1=128, T2=115, T3=183, T4=127; N0=279, N1=70,
N2=204; G1=157, G2=141, G3=255; early EC=110, invasive=443; only surgery=423, adjuvant chemoimmunoradiotherapy-
AT=130: 5-FU+thymalin/taktivin+radiotherapy 45-50Gy). Variables selected for study were input levels of 45 blood
parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method.
Differences in curves between groups of ECP were evaluated using a log-rank test. Regression, multivariate Cox
modeling, multi-factor clustering, discriminant analysis, structural equation modeling, Monte Carlo, bootstrap
simulation and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 1880.1±2226.6 days and cumulative 5-year survival (5YS) reached 52%, 10 years
– 45.6%, 20 years – 33.4%. AT significantly improved 5YS (67.9% vs. 48.5%) (P=0.00039 by log-rank test). Regression
modeling displayed EC cell dynamics significantly depended on: phase transition (PT) N0—N12 in terms of synergetics,
histology, G, EC growth, age, gender, localization, Hb, blood cells, glucose, residual nitrogen (P=0.000-0.033). Neural
networks simulation revealed relationships between EC cell dynamics and blood ESS (rank=1), segmented neutrophils
(2), age (3), Hb (4), leucocytes (5), monocytes (6), lymphocytes (7), protein (8), erythrocytes (9), thrombocytes (10), stick
neutrophils (11), eosinophils (12). Prediction was 87-91% by neural networks computing.
CONCLUSIONS: Esophageal cancer cell dynamics significantly depended on blood cell circuit, biochemical factors,
hemostasis system, cancer characteristics, anthropometric data.

4.
DATA:
Males…………………………………….…………………………..…….413
Females…….......................................................................................140
Age=56.5±8.9 years Tumor Size=6±3.5 cm
Only Surgery.…..................................................................................423
Adjuvant Chemoimmunoradiotherapy (5FU + thymalin/taktivin, 5-6
cycles+ Radiotherapy 45-50Gy)........................................................130

5.
RADICAL PROCEDURES (R0):
Esophagogastrectomies Garlock……………………….……………...286
Esophagogastrectomies Lewis..........................................................267
Combined sophagogastrectomies with Resection of Trachea, Aorta,
Liver, Vena Cava Superior, Vena Azygos, Diaphragm, Pancreas,
Colon Transversum, Pericardium, Splenectomy (R0)………….…...153
2 Field Lymph Node Dissection.……………...…………………..….…363
3 Field Lymph Node Dissection…………………………………..…….190
Intrathoracic Esophagogastroanastomosis……………….…………363
Neck Esophagogastroanastomosis……………….…………………..190

6.
SURVIVAL RATE:
5-Year Survivors…………...................................................... 185 (33.4%)
10-Year Survivors……………………………………................ 99 (17.9%)
Losses……………………………………………………………..226 (40.9%)
General Life Span=1880.1±2226.6 days
For 5-Year Survivors=4295.7±2413.5 days
For 10-Year Survivors=5883±2296.6 days
For Losses=628.3±319.9 days
Cumulative 5-Year Survival……..……….........................................52%
Cumulative 10-Year Survival……..…...……………………………...45.6%
Cumulative 20-Year Survival………………………………………....33.4%

7.
GENERAL ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE
ESOPHAGOGASTRECTOMIES (KAPLAN-MEIER) (N=553):
Survival Function
5-Year survival=52%; 10-Year Survival=45.6%; 20-Year Survival=33.4%.
Complete Censored
-5 0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving

8.
RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION EARLY—INVASIVE
CANCER IN PREDICTION OF ESOPHAGEAL PATIENTS SURVIVAL (N=553):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of Early ECP=100%; 5-Year Survival of Invasive ECP=39%
(P=0.000 by Log-Rank Test).
Complete Censored
0 5 10 15 20 25 30 35 40
Years After Esophagogastrectomies
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 Cancer, n=443
Early Cancer, n=110

9.
RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION N0—N1-2 IN
PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=553):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP with N0=73.3%; 5-Year Survival of ECP with N1-2=28.6%
(P=0.000 by Log-Rankn Test).
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
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 N1-2, n=274
ECP wth N0, n=279

10.
RESULTS OF UNIVARIATE ANALYSIS OF ADJUVANT CHEMOIMMUNORADIOTHERAPY IN
PREDICTION OF ESOHAGEAL CANCER PATIENTS SURVIVAL (N=553):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP after AT=67.9%; 5-Year Surival after Surgery=48.5%
(P=0.00039 by Log-Rank Test)
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
Surgery, n=423
AT=130

11.
RESULTS REGRESSION MODELING IN ESOPHAGEAL CANCER DYNAMICS (N=553):
Effect
D - Test of all effects Distribution :
NORMAL Link function: LOG
Degr. of
Freedom
Wald
Stat.
p
Intercept 1 28.61731 0.000000
Hemoglobin 1 14.92816 0.000112
Erythrocytes 1 15.59624 0.000078
Monocytes 1 10.42142 0.001246
Thrombocytes 1 12.09522 0.000506
Glucose 1 6.51270 0.010711
Residual Nitrogen 1 25.89537 0.000000
Stick Neutrophils 1 12.10752 0.000502
Stick Neutrophils abs 1 13.65376 0.000220
Monocytes abs 1 14.87247 0.000115
Age 1 9.49503 0.002060
Blood type 4 23.60901 0.000096
Phase Transition N0--N12 1 31.48910 0.000000
Sex 1 8.23048 0.004119
Histology 2 6.81760 0.033081
G1-3 2 50.16923 0.000000
Tumor Growth 2 13.28298 0.001305
Localization 1 12.46865 0.000414
Esophageal/Cardioesophageal Cancer 1 19.73187 0.000009

12.
GRM RESULTS IN ESOPHAGEAL CANCER DYNAMICS (N=553):
Pareto Chart of t-Values for Coefficients; df=537
Variable: D
Sigma-restricted parameterization
2.200572
2.306073
2.360301
2.475662
2.751244
2.953211
3.215567
3.274652
3.620066
4.282686
5.14579
7.43675
7.832812
8.437223
11.54094
p=.05
t-Value (for Coefficient;Absolute Value)
OPERAT
AGE
CP
H_T
P1_4
FT
MASSA
EC_CEC
CHAR_GR
G1_3
LOC
THR
LOCAL
THR_CC
T
Effect
D
Param.
D
Std.Err
D
t
D
p
Intercept -2.348411.115311 -2.105610.035702
Coler Index -0.297870.126199 -2.360300.018617
Thrombocytes 0.010630.001429 7.436750.000000
Hemorrage Time 0.010540.004258 2.475660.013606
T1-4 1.465280.12696311.540940.000000
Age -0.021350.009260 -2.306070.021487
weight 0.020660.006424 3.215570.001380
G1-3 0.446440.104243 4.282690.000022
Tumor Growth -0.593810.164033 -3.620070.000322
Surgery type -1.173830.533421 -2.200570.028191
Localization 1.086310.138687 7.832810.000000
Phase Transition Early-Invasive Cancer -1.367740.463135 -2.953210.003283
Esophageal/Cardioesophageal Cancer 1.857990.567387 3.274650.001126
Thrombocytes/Cancer cells -0.003190.000378 -8.437220.000000
P1-4 0.492060.178848 2.751240.006137
u3 vs Others -2.004010.389447 -5.145790.000000

13.
RESULTS OF NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL
CANCER DYNAMICS (N=553):
Neural Network : n=533
Baseline Error=0.000;
Area under ROC Curve=1.000;
Correct Classification Rate 100%
Rank Sensitivity
ESS 1 3.1e+77
Seggmented Neutrophils 2 3.8e+49
Age 3 2.7e+39
Hemoglobin 4 2.1e+32
Leucocytes 5 1.02e+30
Monocytes 6 4.4e+27
Lymphocytes 7 1.8e+18
Protein 8 1.2e+17
Erythrocytes 9 5.0e+16
Thrombocytes 10 3.6e+16
Stick Neutrophils 11 3.2e+16
Eosinophils 12 5.3e+15

14.
RESULTS OF BOOTSTRAP SIMULATION IN PREDICTION OF ESOPHAGEAL CANCER
DYNAMICS (N=553):
Bootstrap Simulation n=553
Significant Factors
(Number of Samples=3333)
Rank Kendall’Tau-A P<
Healthy Cells/Cancer Cells 1 -0.835 0.000
Erythrocytes/Cancer Cells 2 -0.778 0.000
Thrombocytes/Cancer Cells 3 -0.710 0.000
Leucocytes/Cancer Cells 4 -0.677 0.000
Segmented Neutrophils/Cancer Cells 5 -0.635 0.000
Lymphocytes/Cancer Cells 6 -0.632 0.000
T1-4 7 0.544 0.000
P1-4 8 0.477 0.000
Monocytes/Cancer Cells 9 -0.459 0.000
PT Early---Invasive Cancer 10 0.317 0.000
PT N0---N12 11 0.276 0.000
Residual Nitrogen 12 0.220 0.000
Combined Procedures 13 -0.203 0.000
Tumor Growth 14 0.191 0.000
Stick Neutrophils/Cancer Cells 15 -0.178 0.000
Esophageal/Cardioesophageal Cancer 16 0.175 0.000
Hemorrhage Time 17 0.163 0.000
Surgery Type 18 0.160 0.000
Protein 19 -0.159 0.000
ESS 20 0.137 0.000
Bilirubin 20 -0.127 0.000
Thrombocytes 21 0.117 0.000
Erythrocytes tot 22 -0.116 0.000
Weight 23 0.097 0.01
AT 24 0.093 0.01
Stick Neutrophils 25 0.086 0.01
Age 26 0.078 0.05
Histology 27 0.075 0.05
Chlorides 28 -0.066 0.05
Color Index 29 -0.065 0.05
Stick Neutrophils tot 30 0.063 0.05

15.
RESULTS OF KOHONEN SELF-ORGANIZING NEURAL NETWORKS COMPUTING IN PREDICTION OF
ESOPHAGEAL CANCER DYNAMICS (N=553):

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ESOPHAGEAL CANCER DYNAMICS IN TERMS OF SYNERGETICS:

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PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS
(N=553):

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PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS
(N=553):

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PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS
(N=553):

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PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS
(N=553):

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PROGNOSTIC SEPATH-MODEL OF ESOPHAGEAL CANCER DYNAMICS
(N=553):

22.
Content of this presentation is copyright and responsibility of the author.
Permission is required for re-use.
Conclusion:
Esophageal cancer cell dynamics significantly depended on:
1) blood cell circuit;
2) biochemical factors;
3) hemostasis system;
4) cancer characteristics;
5) anthropometric data;
6) phase transition early-invasive cancer;
7) phase transition N0---N12;
8) localization;
9) cell ratio factors.

23.
European Society for Medical Oncology (ESMO)
Via Ginevra 4, CH-6900 Lugano
T. +41 (0)91 973 19 00
esmo@esmo.org
esmo.org
● 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