Kshivets wscts2015

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  1. 1. Oleg Kshivets, MD, PhD Surgery Department, Kaluga Cancer Clinical Center, Russia
  2. 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=56.28.8 years; tumor size=6.33.4 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 1776.12223.2 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) N0N12 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. 3. Males.359 Females.........132 Age=56.28.8 years Tumor Size=6.33.4 cm Only Surgery....377 Adjuvant Chemoimmunoradiotherapy (5FU+thymalin/taktivin, 5-6 cycles+ Radiotherapy 45-50Gy)...........................114
  4. 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. 5. T1..90 N0...227 G1136 T2112 N1.....69 G2123 T3166 N2...195 G3232 T4123 M0..491 Adenocarcinoma279 Squamos Cell Carcinoma..202 Mix.............10 Early Cancer.....71 Invasive Cancer...420
  6. 6. Alive...238 (48.5%) 5-Year Survivors...147 (29.9%) 10-Year Survivors...79 (16.1%) Losses.223 (45.4%) General Life Span=1776.12223.2 days For 5-Year Survivors=4382.82559.8 days For 10-Year Survivors=6047.82454.2 days For Losses=630.2320.5 days Cumulative 5-Year Survival.47.1% Cumulative 10-Year Survival...40.3% Cumulative 20-Year Survival...30%
  7. 7. 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 EarlyInvasive 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
  8. 8. Discriminant Function Analysis Summary: Wilks' Lambda: ,50259 approx. F (13,356)=27,102 p