Successfully reported this slideshow.
Your SlideShare is downloading. ×

Kshivets ASCVTS Moscow2018

Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Ad
Upcoming SlideShare
Kshivets yokohama iaslc2017
Kshivets yokohama iaslc2017
Loading in …3
×

Check these out next

1 of 22 Ad
Advertisement

More Related Content

Slideshows for you (20)

Similar to Kshivets ASCVTS Moscow2018 (20)

Advertisement

Recently uploaded (20)

Advertisement

Kshivets ASCVTS Moscow2018

  1. 1. Esophageal Cancer: System Approach Kshivets Oleg, MD, PhD Surgery Department, Roshal Hospital, Roshal, Russia
  2. 2. Esophageal Cancer: System Approach Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia OBJECTIVE: Search of optimal diagnosis and treatment strategies for esophageal cancer (EC) pa­tients (ECP) (T1-4N0-2M0) realized. METHODS: We analyzed data of 515 consecutive ECP (age=56.3±8.9 years; tumor size=6.2±3.4 cm) radically operated (R0) 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 1814.5±2225.6 days and cumulative 5-year survival (5YS) reached 48.8%, 10 years – 42.3%, 20 years – 31.7%. 160 ECP lived more than 5 years (LS=4384.1±2474.1 days), 89 ECP – more than 10 years (LS=5913.1±2360.3 days). 224 ECP died because of EC (LS=629.2±320.1 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) N0—N12 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, blood group, Rh, glucose (P=0.000-0.037). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and healthy cells/CC (rank=1), erythrocytes/CC (2), protein (3), T (4), segmented neutrophils/CC (5), eosinophils/CC (6), stick neutrophils/CC (7), G (8), CC (9), PT early-invasive EC (10), PT N0—N12 (11), localization (12), thrombocytes/CC (13), lymphocytes/CC (14), monocytes/CC (15), prothrombin index (16), leucocytes/CC (17). 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. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with
  3. 3. Data: • Males…………………………………………………………………….380 • Females………..…………………………….....................................135 • Age=56.3±8.9 years • Tumor Size=6.2±3.4 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 G1…………148 •T2……..114 N1…........69 G2…………125 •T3……..175 N2…......198 G3…………242 •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=1814.5±2225.6 days • For 5-Year Survivors=4384.1±2474.1 days • For 10-Year Survivors=5913.1±2360.3 days • For Losses=629.2±320.1 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 Early— Invasive Cancer in Prediction of Esophageal Cancer Patients Survival (n=515):
  9. 9. Results of Univariate Analysis of Phase Transition N0—N1-2 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): ECP=515; Cox Proportional Hazards Results Factors: Parameter Estimate Standard Error Chi-square P value 95% Lower CL 95% Upper CL Hazard Ratio Blood Group 0,20689 0,073286 7,96949 0,004757 0,06325 0,350527 1,229846 Rh-Factor -0,41598 0,178497 5,43097 0,019783 -0,76583 -0,066130 0,659695 Hemorrhage Time 0,00132 0,000426 9,62521 0,001919 0,00049 0,002155 1,001321 Glucose -0,19071 0,084851 5,05136 0,024607 -0,35701 -0,024400 0,826376 Residual Nitrogen 0,05300 0,011885 19,88396 0,000008 0,02970 0,076292 1,054427 Prothrombin Index 0,02341 0,007084 10,92358 0,000949 0,00953 0,037299 1,023690 T1-4 0,28869 0,096365 8,97459 0,002738 0,09982 0,477561 1,334675 N0---N12 0,63361 0,161618 15,36978 0,000088 0,31685 0,950376 1,884404 Age 0,02439 0,007805 9,76377 0,001780 0,00909 0,039685 1,024688 G1-3 0,24259 0,081640 8,82932 0,002964 0,08257 0,402596 1,274540 Adjuvant Chemoimmunoradiotherapy -0,91093 0,201521 20,43288 0,000006 -1,30590 -0,515955 0,402151 Leucocytes (tot) -1,56821 0,380900 16,95066 0,000038 -2,31476 -0,821660 0,208418 Eosinophils (tot) 1,81465 0,431282 17,70363 0,000026 0,96935 2,659945 6,138915 Stick Neutrophils (tot) 1,34835 0,362871 13,80709 0,000203 0,63714 2,059569 3,851080 Segmented Neutrophils (tot) 1,59067 0,383243 17,22707 0,000033 0,83953 2,341815 4,907042 Lymphocytes (tot) 1,58322 0,386595 16,77144 0,000042 0,82551 2,340934 4,870621 Monocytes (tot) 1,30273 0,374977 12,06987 0,000512 0,56779 2,037675 3,679343 Leucocytes/Cancer Cells 1,37589 0,652189 4,45064 0,034888 0,09763 2,654160 3,958610 Eosinophils/Cancer Cells -3,73063 1,566692 5,67018 0,017256 -6,80129 -0,659969 0,023978 Segmented Neutrophils/Cancer Cells -1,54011 0,694547 4,91698 0,026594 -2,90139 -0,178819 0,214359 Lymphocytes/Cancer Cells -1,64546 0,789598 4,34273 0,037167 -3,19305 -0,097877 0,192924 Localization: Upper/3 vs. Others/3 -0,48978 0,194124 6,36565 0,011635 -0,87026 -0,109304 0,612761
  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<0.0000 Factors Wilks' - Lambda Partial - Lambda F-remove - (1,365) p-value Toler. 1-Toler. - (R-Sqr.) Rh-factor 0.465749 0.974809 9.43249 0.002292 0.906600 0.093400 HB 0.468602 0.968873 11.72619 0.000686 0.850765 0.149235 Hemorrhage Time 0.461163 0.984502 5.74568 0.017031 0.892014 0.107986 Residual Nitrogen 0.491681 0.923395 30.28066 0.000000 0.794226 0.205774 Stick Neutrophils (abs) 0.462830 0.980957 7.08579 0.008113 0.021425 0.978575 Segmented Neutrophils (abs) 0.462213 0.982266 6.58971 0.010655 0.119903 0.880097 T1-4 0.480596 0.944693 21.36875 0.000005 0.549885 0.450115 Phase Transition N0---N1-2 0.488041 0.930283 27.35391 0.000000 0.709487 0.290513 G1-3 0.465201 0.975956 8.99241 0.002897 0.867697 0.132303 Tumor Growth 0.469517 0.966985 12.46197 0.000468 0.646569 0.353431 Adjuvant Chemoimmunoradiotherapy 0.480222 0.945429 21.06826 0.000006 0.806219 0.193781 Combined Procedure 0.466634 0.972958 10.14446 0.001572 0.785403 0.214598 Phase Transition Early---Invasive Cancer 0.476821 0.952172 18.33426 0.000024 0.533466 0.466534 Leucocytes (tot) 0.464663 0.977086 8.55995 0.003651 0.000260 0.999740 Eosinophils (tot) 0.461626 0.983514 6.11822 0.013834 0.059994 0.940006 Segmented Neutrophils (tot) 0.465465 0.975402 9.20488 0.002587 0.000461 0.999539 Lymphocytes (tot) 0.464409 0.977622 8.35510 0.004076 0.003106 0.996894 Monocytes (tot) 0.464288 0.977876 8.25781 0.004295 0.029356 0.970644
  14. 14. Results of Neural Networks Computing in Prediction of Esophageal Cancer Patients Survival after Complete esophagogastrectomies (n=384): Correct Classification Rate=100% Error=0.000 Area under ROC Curve=1.000 Factors: Rank Sensitivity Healthy Cells/Cancer Cells Erythrocytes/Cancer Cells Protein T1-4 Segmented Neutrophils/Cancer Cells Eosinophils/Cancer Cells Stick Neutrophils/Cancer Cells G1-3 Tumor Size Phase Transition Early---Invasive Phase Transition N0---N12 Localization Thrombocytes/Cancer Cells Lymphocytes/Cancer Cells Monocytes/Cancer Cells Prothrombin Index Leucocytes/Cancer Cells 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 84570090 77764200 37976840 3958902 3518292 397879 304065 190705 40263 10246 9281 1107 140 64 10 5 1
  15. 15. Results of Bootstrap Simulation in Prediction of esophageal Cancer Patients Survival after esophagogastrectomies (n=384): Significant Factors (Number of Samples=3333) Rank Kendal Tau-A P Tumor Size 1 -0.290 0.000 Healthy Cells/Cancer Cells 2 0.288 0.000 T1-4 3 -0.280 0.000 Erythrocytes/Cancer Cells 4 0.278 0.000 Leucocytes/Cancer Cells 5 0.268 0.000 Thrombocytes/Cancer Cells 6 0.265 0.000 Lymphocytes/Cancer Cells 7 0.259 0.000 Segmented Neutrophils/Cancer Cells 8 0.249 0.000 Residual Nitrogen 9 -0.243 0.000 Phase Transition N0---N12 10 -0.228 0.000 Monocytes/Cancer Cells 11 0.223 0.000 Hemorrhage Time 12 -0.223 0.000 Phase Transition Early---Invasive Cancer 13 -0.189 0.000 Eosinophils/Cancer Cells 14 0.163 0.000 Chlorides 15 0.162 0.000 Stick Neutrophils/Cancer Cells 16 0.152 0.000 Tumor Growth 17 -0.131 0.000 G1-3 18 -0.128 0.000 Glucose 19 0.087 0.05 Erythrocytes 20 0.080 0.05 Weight 21 0.080 0.05 Localization 22 0.075 0.05 Prothrombin Index 22 -0.073 0.05
  16. 16. Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of esophageal Cancer Patients Survival after Complete esophagogastrectomies (n=384):
  17. 17. Esophageal Cancer Dynamics:
  18. 18. Prognostic Equation Models of Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=384):
  19. 19. Prognostic SEPATH-Model of Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=384):
  20. 20. 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 Chemoimmunoradiotherapy; 8) Cancer Characteristics ; 9) Tumor Localization; 10) Anthropometric Data. Conclusion:
  21. 21. Optimal Diagnosis and Treatment Strategies for Esophageal Cancer are: 1) Screening and Early Detection of Esophageal Cancer; 2) Availability of Experienced Thoracoabdominal Surgeons because of Complexity of Radical Procedures; 3) Aggressive en block Surgery and Adequate Lymph Node Dissection for Completeness; 4) Precise Prediction; 5) Adjuvant Chemoimmunoradiotherapy for Esophageal Cancer Patients with Unfavorable Prognosis. Conclusion:
  22. 22. 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

×