Kshivets astana wscts2017

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  1. 1. ESOPHAGEAL CANCER: SURGERY AND PRECISE PROGNOSIS Kshivets Oleg, MD, PhD Surgery Department, Roshal Hospital, Roshal, Moscow, Russia
  2. 2. ABSTRACT ESOPHAGEAL CANCER: SURGERY AND PRECISE PROGNOSIS BACKGROUND: We examined factors in terms of precise prognosis of 5-year survival (5YS) of esophageal cancer (EC) patients (ECP) (T1-4N0-2M0) after complete (R0) esophagogastrectomies (EG). METHODS: We analyzed data of 515 consecutive ECP (age=56.38.9 years; tumor size=6.23.4 cm) radically operated and monitored in 1975-2017 (m=380, f=135; esophagogastrectomies (EG) Garlock=280, EG Lewis=235, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium, splenectomy=151; adenocarcinoma=292, squamous=213, mix=10; T1=101, T2=114, T3=175, T4=125; N0=248, N1=69, N2=198; G1=148, G2=125, G3=242; early EC=82, invasive=433; only surgery=394, adjuvant chemoimmunoradiotherapy-AT=121: 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 (LS) was 1814.52225.6 days and cumulative 5YS reached 48.8%, 10 years 42.3%, 20 years 31.7%. 160 ECP lived more than 5 years (LS=4384.12474.1 days), 89 ECP more than 10 years (LS=5913.12360.3 days). 224 ECP died because of EC (LS=629.2320.1 days). AT significantly improved 5YS (67.6% vs. 44.6%) (P=0.00008 by log-rank test). Cox modeling displayed that 5YS of ECP significantly depended on: phase transition (PT) N0N12 in terms of synergetics, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), T, G, age, AT, localization, blood cells, prothrombin index, coagulation time, residual nitrogen , RH (P=0.000-0.026). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and healthy cells/CC (rank=1), PT early-invasive EC (rank=2), thrombocytes/CC (3), PT N0N12 (4), erythrocytes/CC (5), stick neutrophils/CC (6), segmented neutrophils/CC (7), lymphocytes/CC (8), leucocytes/CC (9), eosinophils/CC (10), monocytes/CC (11) . Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0 ). CONCLUSIONS: 5YS of ECP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0-- N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor localization; 10) anthropometric data.
  3. 3. DATA: Males.380 Females.......................................135 Age=56.38.9 years Tumor Size=6.23.4 cm Only Surgery...................................394 Adjuvant Chemoimmunoradiotherapy (5FU+thymalin/taktivin, 5-6 cycles+ Radiotherapy 45-50Gy)....121
  4. 4. RADICAL PROCEDURES: Esophagogastrectomies Lewis (R0)...235 Esophagogastrectomies Garlock (R0)................................280 Combined Esophagogastrectomies with Resection of Pancreas, Liver, Trachea, Lung, Aorta, Vena Cava Superior, Colon Transversum, Diaphragm, Pericardium, Splenectomy (R0).151 2-Field Lymphadenectomy....364 3-Field Lymphadenectomy....151
  5. 5. STAGING: T1..101 N0..248 G1148 T2..114 N1........69 G2125 T3..175 N2......198 G3242 T4..125 M0...515 Adenocarcinoma..292 Squamos Cell Carcinoma..213 Mix....................10 Early Cancer.....82 Invasive Cancer.....433
  6. 6. SURVIVAL RATE: Alive............................260 (50.5%) 5-Year Survivors............160 (31.1%) 10-Year Survivors...........................89 (17.3%) Losses...224 (43.5%) General Life Span=1814.52225.6 days For 5-Year Survivors=4384.12474.1 days For 10-Year Survivors=5913.12360.3 days For Losses=629.2320.1 days Cumulative 5-Year Survival.48.8% Cumulative 10-Year Survival...42.3% Cumulative 20-Year Survival...31.7%
  7. 7. GENERAL ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (KAPLAN-MEIER) (N=515):
  8. 8. RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION EARLYINVASIVE CANCER IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=515):
  9. 9. RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION N0N1-2 IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=515):
  10. 10. RESULTS OF UNIVARIATE ANALYSIS OF ADJUVANT CHEMOIMMUNORADIOTHERAPY IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=515):
  11. 11. RESULTS OF UNIVARIATE ANALYSIS OF LOCALIZATION (UPPER/3 VS. MIDDLE/3 & LOWER/3) IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=515):
  12. 12. RESULTS OF COX REGRESSION MODELING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=515): Cox Regression: Factors Parameter Estimate Standard Error Chi- square P value 95% Lower CL 95% Upper CL Hazard Ratio Rh-factor -0.45229 0.176756 6.54776 0.010502 -0.79873 -0.105858 0.636168 Hemorrhage Time 0.00126 0.000433 8.40139 0.003749 0.00041 0.002105 1.001257 Glucose -0.18331 0.084425 4.71444 0.029910 -0.34878 -0.017840 0.832511 Residual Nitrogen 0.05237 0.011983 19.10326 0.000012 0.02889 0.075860 1.053770 Protein 0.02949 0.009120 10.45502 0.001223 0.01161 0.047361 1.029926 Prothrombin Index 0.02483 0.007028 12.48251 0.000411 0.01106 0.038606 1.025142 T1-4 0.38912 0.098018 15.76015 0.000072 0.19701 0.581233 1.475684 Phase Transition N0---N1-2 0.64369 0.165528 15.12176 0.000101 0.31926 0.968115 1.903483 Age 0.03037 0.008013 14.36858 0.000150 0.01467 0.046077 1.030839 Histology -0.29687 0.131185 5.12126 0.023634 -0.55399 -0.039757 0.743137 G1-3 0.40780 0.091366 19.92147 0.000008 0.22872 0.586871 1.503502 Adjuvant Chemoimmunoradiotherapy -0.85863 0.200235 18.38792 0.000018 -1.25108 -0.466177 0.423742 Leucocytes (tot) -1.47405 0.367150 16.11886 0.000059 -2.19365 -0.754444 0.228997 Eosinophils (tot) 1.84217 0.421596 19.09271 0.000012 1.01586 2.668487 6.310240 Stick Neutrophils (tot) 1.26769 0.347754 13.28861 0.000267 0.58610 1.949274 3.552630 Segmented Neutrophils (tot) 1.49871 0.369391 16.46123 0.000050 0.77472 2.222700 4.475901 Leucocytes/Cancer Cells 1.43528 0.626593 5.24687 0.021986 0.20718 2.663375 4.200804 Eosinophils/Cancer Cells -4.02473 1.558966 6.66499 0.009832 -7.08024 -0.969211 0.017868 Segmented Neutrophils/Cancer Cells -1.59111 0.666185 5.70439 0.016923 -2.89680 -0.285408 0.203700 Lymphocytes/Cancer Cells -1.68907 0.762446 4.90766 0.026738 -3.18343 -0.194699 0.184692 Lymphocytes (tot) 1.47963 0.374498 15.61013 0.000078 0.74563 2.213633 4.391320 Monocytes (tot) 1.17235 0.358303 10.70567 0.001068 0.47009 1.874612 3.229575 Localization: Upper/3 vs. Others/3 -0.53733 0.196847 7.45108 0.006340 -0.92314 -0.151514 0.584309
  13. 13. RESULTS OF DISCRIMINANT FUNCTION ANALYSIS IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=384): Discriminant Function Analysis Summary Wilks' Lambda: .45402 approx. F (18,365)=24.385 p