Kshivets O. Esophagogastric Cancer Surgery

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ARTIFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN OPTIMIZATION OF TREATMENT FOR ESOPHAGOGASTRIC CANCER PATIENTS

Text of Kshivets O. Esophagogastric Cancer Surgery

  • ARTIFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN OPTIMIZATION OF TREATMENT FOR ESOPHAGOGASTRIC CANCER PATIENTS Oleg Kshivets, MD, PhD Department of Surgery, Siauliai Public Hospital & Cancer Center, Siauliai, Lithuania The 2006 Gastrointestinal Cancers Simposium, January 26-28, 2006, San Francisco, CA, the USA
  • Abstract ARTFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN OPTIMIZATION OF TREATMENT FOR ESOPHAGOGASTRIC CANCER PATIENTS Oleg Kshivets Department of Surgery, Siauliai Public Hospital & Cancer Center, Siauliai, Lithuania
    • OBJECTIVE: The search of optimal treatment plan for esophagogastric cancer (EGC) patients (EGCP) with stage T1-4N1-3M0 was realized. We examined the clinicomorphologic factors associated with the low- and high-risk of generalization of EGCP after complete en block (R0) esophagogastrectomies (EG) through left and right thoracoabdominal incision. METHODS: We analyzed data of 187 consecutive EGCP (age=55.78.8 years; tumor size=6.83.3 cm) radically operated and monitored in 1975-2005 (males=138, females=49; EG Ivor-Lewis=60, EG Garlock=127; combined EG with resection of pancreas, liver, diaphragm, colon transversum, splenectomies=74; lymphadenectomy D2=80, D3=107; adenocarcinoma=109, squamos=68, mix=10; T1=27, T2=43, T3=67, T4=50; N0=75, N1=24, N2=85; N3=3; G1=54, G2=41, G3=92; only surgery-S=154, adjuvant chemoimmunotherapy-AT=33: 5-FU + thymalin/taktivin). Variables selected for 5-year survival (5YS) 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 CECP were evaluated using a log-rank test. 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: General cumulative 5YS was 34.9%, 10-year survival 26.1%. 72 EGCP (38.5%) were alive, 39 EGCP (life span: LS=3699.71617.6 days) lived more than 5 years without any features of CEC progressing. LS for AT was 2255.9211.7 days, for S 1324.81550.4 days (P=0.032, by log-rank test P=0.036). Cox modeling displayed that 5YS of EGCP (n=187) after complete EG significantly depended on: combined procedures, age, blood cell subpopulations, cell ratio factors, lymphoid infiltration of EGC, T (P=0.000-0.029). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS of EGCP and combined procedures (rank=1), lymphoid infiltration of EGC (2), EGC growth (3), T1-4 (4), histology (5), G1-3 (6), N0-3 (7), procedure type (8), gender (9), Rh-factor (10), blood coagulation time (11), blood lymphocytes (12), protein (13), neutrophils (14), age (15), blood leucocytes (16), tumor size (17), ESS (18), blood chlorides (19), prothrombin index (20). Correct prediction of EGCP survival after radical procedures was 91.7% by logistic regression (odds ratio=98.8), 92.4% by discriminant analysis and 100% by neural networks computing (area under ROC curve=1.0; error=0.0018). CONCLUSIONS: Optimal treatment strategies for EGCP are: 1) screening and early detection of EGC; 2) aggressive en block surgery for completeness; 3) precise prediction; 4) AT for EGCP with unfavorable prognosis.
  • Factors:
    • 1) Antropometric Factors.. 4
    • 2) Blood Analysis.. 26
    • 3) Hemostasis Factors.... 3
    • 4) Cell Ratio Factors... 9
    • 6) Esophagogastric Cancer Characteristics... 12
    • 7) Biochemic Factors... 7
    • 8) Treatment Characteristics.. 3
    • 9) Survival Data 4
    • In All.. 68
  • Main Problem of Analysis of Alive Supersystems including Combinatorial Optimization (e.g. Esophagogastric Cancer Patient Homeostasis, Search of Optimal Treatment Plan ): Phenomenon of Combinatorial Explosion
    • Number of Clinicomorphological Factors:..... 68
    • Number of Possible Combination for Random Search:.. n!=68!=2.48e+96
    • Operation Time of IBM Blue Gene/L Supercomputer (135.5TFLOPS) 5.8e+74 Years
    • The Age of Our Universe..... 1.3e+10 Years
  • Basis:
    • NP RP P
    • n! n*n*2(e+n) or n log n n
    • AI CSA+S+B SM
    • AI - Artificial Intelligence
    • CSA - Complex System Analysis
    • S - Statistics
    • B - biometrics
    • SM - simulation modeling
  • Data:
    • Males 138
    • Females.. 49
    • Age= 55.78.8 years
    • Tumor Size= 6.83.3 cm
    • Only Surgery. 154
    • Adjuvant Chemoimmunotherapy (5FU+thymalin/taktivin, 5-6 cycles).. 33
  • Radical Procedures:
    • Ivor-Lewis Esophagogastrectomies .. 60
    • Garlock Esophagogastrectomies ..... 127
    • Combined Esophagogastrectomies with Resection of Diaphragm, Liver, Mesocolon, Colon Transversum, Splenectomy, Left Hemipancreatectomy, etc. 74
    • Lymphadenectomy D2... 80
    • Lymphadenectomy D3. 107
    • At All.187
  • Schemas of Procedures:
  • Staging:
    • T127 N0....75 G154
    • T243 N124 G241
    • T367 N285 G392
    • T450 N3..3
    • Adenocarcinoma.............109
    • Squamos Cell Carcinoma....68
    • Mixed Carcinoma......10
  • Survival:
    • Alive.... 72 (38.5%)
    • 5-Year Survivors.... 39 (20.9%)
    • 10-Year Survivors... 18 (9.6%)
    • Losses from Cancer. 115 (61.5%)
    • General Life Span= 1276.1 108.3 days
    • Life Span of 5-Year Survivors= 3699.71617.6 days
    • Life Span after Surgery= 1324.81550.4 days
    • Life Span after Ad.CHIT= 2255.9211.7211.7 days
    • Cumulative 5-Year survival=34.9%
    • Cumulative 10-Year survival=26.1%
  • General Esopagogastric Cancer Patients Survival after Complete Ivor-Lewis & Garlock Esophagogastrectomies (Kaplan-Meier) ( n=187 )
  • Results of Univariate Analysis in Prediction of Esopagogastric Cancer Patients Survival ( n=187 )
  • Results of Cox Regression Modeling in Prediction of Esophagogastric Cancer Patients Survival after Complete Esophagogastrectomies (n=187 )
    • Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper
    • Leucocytes abs 11.996 1 0.001 4.8e+13 8.7e+5 2.7e+21
    • Seg.Neutrophils% 7.798 1 0.005 1.738 1.179 2.563
    • Lymphocytes% 5.827 1 0.016 1.617 1.095 2.387
    • Monocytes% 8.264 1 0.004 1.862 1.219 2.845
    • Bilirubin 3.800 1 0.051 1.048 1.000 1.099
    • Eosinophils abs 7.457 1 0.006 0.000 0.000 0.002
    • St.Neutrophils abs 9.553 1 0.001 0.000 0.000 0.000
    • Seg.Neutrophils abs 12.067 1 0.001 0.000 0.000 0.000
    • Lymphocytes abs 10.007 1 0.002 0.000 0.000 0.000
    • Monocytes abs 15.659 1 0.000 0.000 0.000 0.000
    • Age 12.119 1 0.000 1.051 1.022 1.081
    • Sex 2.395 1 0.122 1.543 0.891 2.672
  • Results of Cox Regression Modeling in Prediction of Esophagogastric Cancer Patients Survival after Complete Esophagogastrectomies (n=187 )
    • Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper
    • T 6.572 3 0.087
    • T(1) 0.209 1 0.647 0.698 0.149 3.265
    • T(2) 5.459 1 0.019 0.340 0.138 0.841
    • T(3) 3.636 1 0.057 0.514 0.259 1.019
    • N 1.225 3 0.747
    • N(1) 1.000 1 0.317 2.491 0.416 14.900
    • N(2) 0.631 1 0.427 2.115 0.333 13.436
    • N(3) 0.659 1 0.417 2.096 0.351 12.520
    • Histology 2.706 2 0.258
    • Histology(1) 1.873 1 0.171 2.677 0.653 10.969
    • Histology (2) 2.595 1 0.107 3.313 0.771 14.229
    • G 4.427 2 0.109
  • Results of Cox Regression Modeling in Prediction of Esophagogastric Cancer Patients Survival after Complete Esophagogastrectomies (n=187 )
    • Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper
    • G(1) 3.359 1 0.067 0.593 0.339 1.037
    • G(2) 3.503 1 0.061 0.526 0.268 1.031
    • LIT 26.856 3 0.000
    • LIT(1) 24.975 1 0.000 10.470 4.168 26.299
    • LIT(2) 22.481 1 0.000 7.398 3.235 16.919
    • LIT(3) 8.040 1 0.005 3.133 1.423 6.897
    • Growth 8.125 2 0.017
    • Growth(1) 7.010 1 0.008 4.454 1.474 13.458
    • Growth(2) 3.339 1 0.068 2.835 0.927 8.672
    • Ad.CHIT 0.053 1 0.818 0.925 0.477 1.795
    • Comb.Operation 15.642 7 0.029
    • Comb.Operation(1) 0.277 1 0.598 1.898 0.175 20.619
    • Comb.Operation(2) 0.106 1 0.744 0.836 0.285 2.452