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Kshivets esmo2021

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Kshivets esmo2021

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Esophageal cancer cell dynamics significantly depended on blood cell circuit, biochemical factors, hemostasis system, cancer characteristics, anthropometric data.

Esophageal cancer cell dynamics significantly depended on blood cell circuit, biochemical factors, hemostasis system, cancer characteristics, anthropometric data.

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Kshivets esmo2021

  1. 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. 2. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. DECLARATION OF INTERESTS Oleg Kshivets No disclosures Oleg Kshivets
  3. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 15. RESULTS OF KOHONEN SELF-ORGANIZING NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL CANCER DYNAMICS (N=553):
  16. 16. ESOPHAGEAL CANCER DYNAMICS IN TERMS OF SYNERGETICS:
  17. 17. PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS (N=553):
  18. 18. PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS (N=553):
  19. 19. PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS (N=553):
  20. 20. PROGNOSTIC EQUATION MODELS OF ESOPHAGEAL CANCER DYNAMICS (N=553):
  21. 21. PROGNOSTIC SEPATH-MODEL OF ESOPHAGEAL CANCER DYNAMICS (N=553):
  22. 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. 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

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