Kshivets wscts2015
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Transcript of Kshivets wscts2015
ARTIFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN PRECISE PREDICTION OF 5-YEAR SURVIVAL OF ESOPHAGEAL CANCER PATIENTS AFTER COMPLETE ESOPHAGOGASTRECTOMIES
Oleg Kshivets, MD, PhD
Surgery Department, Kaluga Cancer Clinical Center, Russia
ABSTRACTArtificial Intelligence, System Analysis and Simulation Modeling in Precise Prediction of 5-Year Survival of Esophageal Cancer Patients after Complete EsophagogastrectomiesOleg 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.
DATA: 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
RADICAL PROCEDURES: 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
STAGING: 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
SURVIVAL RATE: 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%
GENERAL ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (KAPLAN-MEIER) (N=491):
RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION EARLY—INVASIVE CANCER IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=491):
RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION N0—N1-2 IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=491):
RESULTS OF UNIVARIATE ANALYSIS OF ADJUVANT CHEMOIMMUNORADIOTHERAPY IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=491):
RESULTS OF UNIVARIATE ANALYSIS OF LOCALIZATION (UPPER/3 VS. MIDDLE/3 & LOWER/3) IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=491):
RESULTS OF COX REGRESSION MODELING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=491):
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
RESULTS OF DISCRIMINANT FUNCTION ANALYSIS IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=370):
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
RESULTS OF NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=370):
Corect Classification Rate=100%Error=0.000Area under ROC Curve=1.000
Factors: Rank Sensitivity
Phase Transition N0---N12 1 311
T1-4Adjuvant ChemoimmunoradiotherapyG1-3Prothrombin IndexGlucoseErythrocytesLocalizationPhase Transition Early---Invasive Cancer
2 3456789
294 22421719015214510864
MonocytesEosinophils/Cancer CellsStick Neutrophils/Cancer Cells
10 1112
23 129
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
RESULTS OF BOOTSTRAP SIMULATION IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER ESOPHAGOGASTRECTOMIES (N=370):
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
Monocytes/Cancer Cells 10 0.207 0.000
Hemorrhage Time 11 -0.201 0.000
Phase Transition Early---Invasive Cancer 12 -0.179 0.000
Stick Neutrophils/Cancer Cells 13 0.159 0.000
Chlorides 14 0.157 0.000
Eosinophils/Cancer Cells 15 0.144 0.000
Tumor Growth 16 -0.121 0.001
G1-3 17 -0.118 0.001
Erythrocytes 18 0.086 0.05
Glucose 19 0.085 0.05
Prothrombin Index 20 -0.081 0.05
Localization 21 0.079 0.05
Weight 22 0.076 0.05
RESULTS OF KOHONEN SELF-ORGANIZING NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=370):
PROGNOSTIC SEPATH-MODEL OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE
ESOPHAGOGASTRECTOMIES (N=370):
5-YEAR SURVIVAL OF ESOPHAGEAL CANCER PATIENTS AFTER RADICAL PROCEDURES SIGNIFICANTLY DEPENDED ON: 1) PHASE TRANSITION “EARLY-INVASIVE CANCER”; 2) PHASE TRANSITION N0--N12; 3) CELL RATIO FACTORS; 4) BLOOD CELL CIRCUIT; 5) BIOCHEMICAL FACTORS; 6) HEMOSTASIS SYSTEM; 7) ADJUVANT CHEMOTHERAPY; 8) TUMOR CHARACTERISTICS AND
LOCALIZATION.
Conclusion:
ADDRESS:
OLEG KSHIVETS, M.D.,PH.D.
CONSULTANT THORACIC, ABDOMINAL, GENERAL SURGEON & SURGICAL ONCOLOGIST
e-mail: [email protected] skype: okshivets http: //www.ctsnet.org/home/okshivets