Artificial Intelligence, System Analysis and Simulation Modeling in Precise Prediction of 5-Year Survival of Esophageal Cancer Patients after Complete Esophagogastrectomies

1. Oleg Kshivets, MD, PhD
Surgery Department, Kaluga Cancer
Clinical Center, Russia

2. ABSTRACT
Artificial Intelligence, System Analysis and Simulation Modeling in Precise Prediction of
5-Year Survival of Esophageal Cancer Patients after Complete Esophagogastrectomies
Oleg Kshivets
OBJECTIVE: We examined factors in terms of precise prediction of 5-year survival (5YS) of
esophageal cancer (EC) patients (ECP) (T1-4N0-2M0) after complete (R0) esophagogastrectomies (EG).
METHODS: We analyzed data of 491 consecutive ECP (age=56.2±8.8 years; tumor size=6.3±3.4 cm)
radically operated and monitored in 1975-2015 (m=359, f=132; EG Garlock=280, EG Lewis=211,
combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung,
trachea, pericardium, splenectomy=147; adenocarcinoma=279, squamous=202, mix=10; T1=90, T2=112,
T3=166, T4=123; N0=227, N1=69, N2=195; G1=136, G2=123, G3=232; early EC=71, invasive=420; only
surgery=377, adjuvant chemoimmunoradiotherapy-AT=114: 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 was 1776.1±2223.2 days and cumulative 5-year survival (5YS) reached
47.1%, 10 years – 40.3%, 20 years – 30%. 147 ECP lived more than 5 years, 79 – 10 years. 223 ECP died
because of EC. Cox modeling displayed (Chi2=293.38, df=18, P=0.000) that 5YS of ECP significantly
depended on: phase transition (PT) N0—N12 in terms of synergetics, cell ratio factors (CRF) (ratio
between cancer cells and blood cells subpopulations), T, G, age, AT, localization, blood cells,
prothrombin index, coagulation time, residual nitrogen (P=0.000-0.014). Neural networks, genetic
algorithm selection and bootstrap simulation revealed relationships between 5YS and PT N0--N12
(rank=1), T, AT, G, prothrombin index, glucose, blood cells, localization, PT early-invasive EC, CRF.
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) CRF; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis
system; 7) adjuvant chemotherapy; 8) tumor characteristics and localization.

3.  Males…………………………………………….359
 Females………..…………………………….......132
 Age=56.2±8.8 years
 Tumor Size=6.3±3.4 cm
 Only Surgery.…………………………………...377
 Adjuvant Chemoimmunoradiotherapy
 (5FU+thymalin/taktivin, 5-6 cycles+ Radiotherapy
 45-50Gy)………………………...........................114

4.  Esophagogastrectomies Lewis (R0)……………211
 Esophagogastrectomies Garlock (R0)………....280
 Combined Esophagogastrectomies with Resection
 of Pancreas, Liver, Trachea, Lung, Aorta, Vena
 Cava Superior, Colon Transversum, Diaphragm,
Pericardium, Splenectomy (R0)…………….....147
 2-Field Lymphadenectomy…………………….364
 3-Field Lymphadenectomy.……………………127

5.  T1……..90 N0..….227 G1…………136
 T2……112 N1….....69 G2…………123
 T3……166 N2…...195 G3…………232
 T4……123 M0…..491
 Adenocarcinoma……………………………279
 Squamos Cell Carcinoma…………………..202
 Mix………………….....…………………........10
 Early Cancer……………………………...…..71
 Invasive Cancer…………………………..….420

6.  Alive………………………………………...238 (48.5%)
 5-Year Survivors…………..……………….147 (29.9%)
 10-Year Survivors…………………………...79 (16.1%)
 Losses……………………………………….223 (45.4%)
 General Life Span=1776.1±2223.2 days
 For 5-Year Survivors=4382.8±2559.8 days
 For 10-Year Survivors=6047.8±2454.2 days
 For Losses=630.2±320.5 days
 Cumulative 5-Year Survival…………………….47.1%
 Cumulative 10-Year Survival…………………...40.3%
 Cumulative 20-Year Survival…………………...30%

12. Cox Regression: Chi2 = 293,38; df = 18; P = 0,0000
Factors: Beta Standard
- Error
t-value Wald -
Statist.
P Risk
ratio
Segmented Neutrophils (%) 0,06904 0,019857 3,47683 12,08835 0,000508 1,07148
Hemorrhage Time 0,00161 0,000407 3,95875 15,67167 0,000076 1,00161
Residual Nitrogen 0,05555 0,012072 4,60139 21,17282 0,000004 1,05712
Prothrombin Index 0,02379 0,006833 3,48133 12,11967 0,000500 1,02407
Segmented Neutrophils (abs) -0,29839 0,108834 -2,74169 7,51684 0,006116 0,74201
Lymphocytes (abs) 0,87499 0,279575 3,12972 9,79513 0,001751 2,39885
Phase Transition N0---N1-2 0,60876 0,158391 3,84337 14,77148 0,000122 1,83814
Age 0,01975 0,007759 2,54520 6,47805 0,010926 1,01995
G1-3 0,25393 0,083591 3,03780 9,22823 0,002385 1,28909
Adjuvant Chemoimmunoradiotherapy -1,01275 0,207721 -4,87554 23,77090 0,000001 0,36322
Phase Transition Early—Invasive Cancer 0,30738 0,564374 0,54464 0,29664 0,586003 1,35986
Eosinophils (tot) 0,49432 0,149800 3,29984 10,88897 0,000968 1,63938
Leucocytes/Cancer Cells -3,01478 1,102960 -2,73335 7,47123 0,006273 0,04906
Stick Neutrophils/Cancer Cells 3,71584 1,141413 3,25548 10,59811 0,001133 41,09317
Segmented Neutrophils/Cancer Cells 2,84619 1,116486 2,54924 6,49861 0,010800 17,22201
Lymphocytes/Cancer Cells 2,62863 1,141840 2,30210 5,29967 0,021336 13,85481
Monocytes/Cancer Cells 4,59519 1,225403 3,74994 14,06208 0,000177 99,00706
Localization: Upper/3 vs. Others/3 -0,38786 0,195170 -1,98728 3,94929 0,046900 0,67851

13. Discriminant Function Analysis Summary: Wilks' Lambda: ,50259 approx. F (13,356)=27,102 p<0,0000
Factors: Wilks'
Lambda
Partial
Lambda
F-remove
(1,356)
p-value Toler. 1-Toler.
(R-Sqr.)
Phase Transition N0---N1-2 0,527146 0,953418 17,39330 0,000038 0,800697 0,199303
T1-4 0,526761 0,954115 17,12054 0,000044 0,614592 0,385408
Prothrombin Index 0,514526 0,976803 8,45443 0,003870 0,925757 0,074243
Residuel Nitrogen 0,538135 0,933949 25,17715 0,000001 0,821853 0,178147
Phase Transition Early---Invasive Cancer 0,527284 0,953169 17,49095 0,000036 0,605391 0,394609
Adjuvant Chemoimmunoradiotherapy 0,527790 0,952255 17,84942 0,000030 0,864724 0,135276
Combined Procedures 0,511148 0,983257 6,06192 0,014286 0,826192 0,173808
Hemorrhage Time 0,516423 0,973214 9,79824 0,001891 0,910109 0,089891
Monocytes (%) 0,511187 0,983183 6,08916 0,014071 0,333019 0,666981
Lymphocytes (%) 0,509637 0,986174 4,99107 0,026099 0,043299 0,956701
Segmented Neutrophils (%) 0,512693 0,980295 7,15602 0,007816 0,041717 0,958283
Hemoglobin 0,514185 0,977450 8,21295 0,004406 0,904335 0,095665
Stick Neutrophils (%) 0,506503 0,992274 2,77170 0,096824 0,398101 0,601899

14. Corect Classification Rate=100%
Error=0.000
Area under ROC Curve=1.000
Factors: Rank Sensitivity
Phase Transition N0---N12 1 311
T1-4
Adjuvant Chemoimmunoradiotherapy
G1-3
Prothrombin Index
Glucose
Erythrocytes
Localization
Phase Transition Early---Invasive Cancer
2
3
4
5
6
7
8
9
294
224
217
190
152
145
108
64
Monocytes
Eosinophils/Cancer Cells
Stick Neutrophils/Cancer Cells
10
11
12
23
12
9
Thrombocytes/Cancer Cells 13 6
Erythrocytes/Cancer Cells 14 4
Segmented Neutrophils/Cancer Cells 15 3.8
Healthy Cells/Cancer Cells 16 3.6
Leucocytes/Cancer Cells 17 1.5
Monocytes/Cancer Cells 18 1.2
Lymphocytes/Cancer Cells 19 1.1

15. Significant Factors (Number of Samples=3333) Rank Kendal Tau-A P
Tumor Size 1 -0.272 0.000
Healthy Cells/Cancer Cells 2 0.270 0.000
T1-4 3 -0.269 0.000
Erythrocytes/Cancer Cells 4 0.261 0.000
Leucocytes/Cancer Cells 5 0.248 0.000
Thrombocytes/Cancer Cells 6 0.247 0.000
Lymphocytes/Cancer Cells 7 0.241 0.000
Segmented Neutrophils/Cancer Cells 8 0.229 0.000
Residual Nitrogen 9 -0.222 0.000
Phase Transition N0---N12 10 -0.213 0.000
Monocytes/Cancer Cells 11 0.207 0.000
Hemorrhage Time 12 -0.201 0.000
Phase Transition Early---Invasive Cancer 13 -0.179 0.000
Stick Neutrophils/Cancer Cells 14 0.159 0.000
Chlorides 15 0.157 0.000
Eosinophils/Cancer Cells 16 0.144 0.000
Tumor Growth 17 -0.121 0.001
G1-3 18 -0.118 0.001
Erythrocytes 19 0.086 0.05
Glucose 20 0.085 0.05
Prothrombin Index 21 -0.081 0.05
Localization 22 0.079 0.05
Weight 23 0.076 0.05

19. Conclusion:

20.  e-mail: okshivets@yahoo.com
 skype: okshivets
 http: //www.ctsnet.org/home/okshivets