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Oleg Kshivets , MD, PhD
Surgery Department, Kaluga Cancer Center, Kaluga, Russia
5-YEAR SURVIVAL OF UPPER THIRD ESOPHAGEAL
CANCER PATIENTS WAS SIGNIFICANTLY SUPERIOR IN
COMPARISON WITH MIDDLE AND LOWER THIRD
ESOPHAGEAL CANCER PATIENTS AFTER RADICAL
SURGERY AND STRONGLY DEPENDED ON PHASE
TRANSITION EARLY-INVASIVE CANCER, LYMPH NODE
METASTASES, CELL RATIO FACTORS AND ADJUVANT
CHEMOIMMUNORADIOTHERAPY
ABSTRACT
5-Year Survival of Upper Third Esophageal Cancer Patients was Significantly
Superior in Comparison with Middle and Lower Third Esophageal Cancer Patients
after Radical Surgery and Strongly Depended on Phase Transition Early-Invasive
Cancer, Lymph Node Metastases, Cell Ratio Factors and Adjuvant
Chemoimmunoradiotherapy
Kshivets Oleg Surgery Department, Kaluga Cancer Center, Russia
OBJECTIVE: This study aimed to determine localization influence of tumor for 5-year survival (5YS) of esophageal (EC) cancer
patients (ECP) after complete en block (R0) esophagogastrectomies (EG) through left/right thoracoabdominal incision.
METHODS: We analyzed data of 428 consecutive patients (age=55.7±8.8 years; tumor size=6.6±3.3 cm) radically operated and
monitored in 1975-2014 (m=320, f=108; EG Garlock=273, EG Lewis=155, combined EG with resection of pancreas, liver, diaphragm,
colon transversum, lung, trachea, pericardium, splenectomy=133; adenocarcinoma=230, squamous=188, mix=10; T1=66, T2=103,
T3=148, T4=111; N0=184, N1=58, N2=186, G1=118, G2=105, G3=205; early cancer=47, invasive cancer=381; upper third=59, middle
& lower third=369, only surgery=341, adjuvant chemoimmunoradiotherapy-AT=87: 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 1675.2±2157.1 days and cumulative 5-year survival (5YS) reached 41.8%, 10 years – 35%, 20
years – 25.1%. 112 patients lived more than 5 years without progression. 216 patients died because of generalization. 5YS of upper third
ECP (55.7%) was significantly superior in comparison with middle & lower third ECP (38.7%) after surgery (P=0.00175 by log-rank
test). Cox modeling displayed that 5YS significantly depended on: phase transition (PT) early-invasive cancer in terms of synergetics, PT
N0--N12, tumor localization, T1-4, G1-3, histology, blood cell subpopulations, age, etc. (P=0.000-0.039). Neural networks, genetic
algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive cancer (rank=1), localization (2),
healthy cells/cancer cells (CC) (3), lymphocytes/CC (4), PT N0--N12 (5), thrombocytes/CC (6), leucocytes/CC (7), erythrocytes/CC (8),
AT (9). Correct prediction of 5YS was 100% by neural networks computing.
CONCLUSIONS: 5YS of upper third ECP was significantly superior in comparison with middle & lower third ECP after radical
procedures and strongly depended on PT early-invasive cancer, lymph node metastases, cell ratio factors and AT.
DATA:
 Males………………………………………………….320
 Females………..………………………………….......108
 Age=55.7±8.8 years
 Tumor Size=6.6±3.3 cm
 Only Surgery.………………………………………...341
 Adjuvant Chemoimmunoradiotherapy
(5FU+thymalin/taktivin, 5-6 cycles+RT 45-50Gy)….87
RADICAL PROCEDURES::
 Left Thoracoabdominal Esophagogastrectomies
(Garlock)……………………..………………………273
 Right Thoracoabdominal Esophagogastrectomies
 (Ivor Lewis)………………….……………………….155
 Combined Esophagogastrectomies with Resection of
Diaphragm, Pericardium, Lung, Liver, Pancreas,
 VCS, Aorta, Splenectomy…………………………...133
 2-Field Lymphadenectomy….………………………302
 3-Field Lymphadenectomy….………………………126
 Upper Third…………………………………………..59
 Middle Third………………………………………….50
 Lower Third…………………………………………271
 Total Esophagus………………………………………48
STAGING:
 T1…….66 N0..….184 G1…………118
 T2……103 N1…….58 G2…………105
 T3……148 N2…...186 G3…………205
 T4……111 M1….….0
 Adenocarcinoma…………………………….230
 Squamos Cell Carcinoma…………………..188
 Mix Carcinoma..……………………………...10
 Early Cancer……………………………….…47
 Invasive Cancer……………………………..381
SURVIVAL RATE:
 Alive………………………………………....185 (43.2%)
 5-Year Survivors…………..………………..112 (26.2%)
 10-Year Survivors…………………………...63 (14.7%)
 Losses……………………………………….216 (50.5%)
 General Life Span=1675.2±2157.1 days
 For 5-Year Survivors=4490.8±2592.2 days
 For 10-Year Survivors=6013±2542.9 days
 For Losses=635.2±323.6 days
 Cumulative 5-Year Survival………………..41.8%
 Cumulative 10-Year Survival………………35%
 Cumulative 20-Year Survival………………25.1%
GENERAL ESOPHAGEAL CANCER PATIENTS SURVIVAL
AFTER COMPLETE ESOPHAGOGASTRECTOMIES
(KAPLAN-MEIER) (N=428):
RESULTS OF UNIVARIATE ANALYSIS OF
LOCALIZATION (UPPER/3 VS. MIDDLE/3 & LOWER/3)
IN PREDICTION OF ESOPHAGEAL CANCER
PATIENTS SURVIVAL (N=428):
RESULTS OF UNIVARIATE ANALYSIS OF PHASE
TRANSITION EARLY—INVASIVE CANCER IN
PREDICTION OF ESOPHAGEAL CANCER PATIENTS
SURVIVAL (N=428)
RESULTS OF UNIVARIATE ANALYSIS OF PHASE
TRANSITION N0—N1-2 IN PREDICTION OF
ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):
RESULTS OF UNIVARIATE ANALYSIS OF ADJUVANT
CHEMOIMMUNORADIOTHERAPY IN PREDICTION OF
ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):
RESULTS OF COX REGRESSION MODELING IN PREDICTION
OF ESOPHAGEAL CANCER PATIENTS SURVIVALAFTER
COMPLETE ESOPHAGOGASTRECTOMIES (N=428):
Cox Proportional Hazards Results Chi-square P value
Localization: Upper/3 vs. Others/3 4.27775 0.038614
N0---N12 9.55416 0.001995
T1-4 43.87534 0.000000
Age 9.25605 0.002347
G1-3 27.90780 0.000000
Histology 6.87734 0.008730
Prothrombin Index 12.07929 0.000510
Adjuvant Chemoimmunoradiotherapy 17.65735 0.000026
Phase Transition Early---Invasive Cancer 5.95464 0.014679
Residual Nitrogen 15.07960 0.000103
Protein 8.73003 0.003130
Leucocytes 8.88698 0.002872
Eosinophils 9.38542 0.002187
StickP Neutrophils 9.42220 0.002144
Segmented Neutrophils 8.93026 0.002805
Lymphocytes 8.30869 0.003946
Monocytes 6.14115 0.013207
RESULTS OF NEURAL NETWORKS COMPUTING IN
PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL
AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=328):
Factor Rank Sensitivity
Phase Transition Early---Invasive Cancer 1 38130
Localization 2 11348
Healthy Cells/Cancer Cells 3 7478
Lymphocytes/Cancer Cells 4 6958
Phase Transition N0---N12 5 4853
Thrombocytes/Cancer Cells 6 3260
Leucocytes/Cancer Cells 7 3196
Erythrocytes/Cancer Cells 8 3075
Adjuvant Chemoimmunoradiotherapy 9 1
Corect Classification Rate=100%
Error=0.000
Area under ROC Curve=1.000
RESULTS OF BOOTSTRAP SIMULATION IN PREDICTION OF
ESOPHAGEAL CANCER PATIENTS SURVIVALAFTER
COMPLETE ESOPHAGOGASTRECTOMIES (N=328):
Significant Factors (Number of Samples=3333) Rank Kendal Tau-A P
T1-4 1 -0.245 0.000
Tumor Size 2 -0.239 0.000
Healthy Cells/Cancer Cells 3 0.231 0.000
Erythrocytes/Cancer Cells 4 0.224 0.000
Leucocytes/Cancer Cells 5 0.218 0.000
Lymphocytes/Cancer Cells 6 0.212 0.000
Thrombocytes/Cancer Cells 7 0.199 0.000
Segmented Neutrophils/Cancer Cells 8 0.193 0.000
Phase Transition N0---N12 9 -0.177 0.000
Eosinophils/Cancer Cells 10 0.171 0.000
Residual Nitrogen 11 -0.164 0.000
Monocytes/Cancer Cells 12 0.163 0.000
Coagulation Time 13 -0.162 0.000
Blood Chlorides 14 0.142 0.000
Phase Transition Early---Invasive Cancer 15 -0.133 0.000
G1-3 16 -0.115 0.01
Histology 17 -0.102 0.05
Stick Neutrophils/Cancer Cells 18 0.101 0.05
Tumor Growth 19 -0.093 0.05
Localization (Upper/3 vs. Others) 20 0.079 0.05
RESULTS OF KOHONEN SELF-ORGANIZING NEURAL
NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL
CANCER PATIENTS SURVIVAL AFTER COMPLETE
ESOPHAGOGASTRECTOMIES (N=328):
ESOPHAGEAL CANCER DYNAMICS:
PROGNOSTIC SEPATH-MODEL OF ESOPHAGEAL
CANCER PATIENTS SURVIVALAFTER COMPLETE
ESOPHAGOGASTRECTOMIES (N=328):
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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Kshivets milan2014

  • 1. Oleg Kshivets , MD, PhD Surgery Department, Kaluga Cancer Center, Kaluga, Russia 5-YEAR SURVIVAL OF UPPER THIRD ESOPHAGEAL CANCER PATIENTS WAS SIGNIFICANTLY SUPERIOR IN COMPARISON WITH MIDDLE AND LOWER THIRD ESOPHAGEAL CANCER PATIENTS AFTER RADICAL SURGERY AND STRONGLY DEPENDED ON PHASE TRANSITION EARLY-INVASIVE CANCER, LYMPH NODE METASTASES, CELL RATIO FACTORS AND ADJUVANT CHEMOIMMUNORADIOTHERAPY
  • 2. ABSTRACT 5-Year Survival of Upper Third Esophageal Cancer Patients was Significantly Superior in Comparison with Middle and Lower Third Esophageal Cancer Patients after Radical Surgery and Strongly Depended on Phase Transition Early-Invasive Cancer, Lymph Node Metastases, Cell Ratio Factors and Adjuvant Chemoimmunoradiotherapy Kshivets Oleg Surgery Department, Kaluga Cancer Center, Russia OBJECTIVE: This study aimed to determine localization influence of tumor for 5-year survival (5YS) of esophageal (EC) cancer patients (ECP) after complete en block (R0) esophagogastrectomies (EG) through left/right thoracoabdominal incision. METHODS: We analyzed data of 428 consecutive patients (age=55.7±8.8 years; tumor size=6.6±3.3 cm) radically operated and monitored in 1975-2014 (m=320, f=108; EG Garlock=273, EG Lewis=155, combined EG with resection of pancreas, liver, diaphragm, colon transversum, lung, trachea, pericardium, splenectomy=133; adenocarcinoma=230, squamous=188, mix=10; T1=66, T2=103, T3=148, T4=111; N0=184, N1=58, N2=186, G1=118, G2=105, G3=205; early cancer=47, invasive cancer=381; upper third=59, middle & lower third=369, only surgery=341, adjuvant chemoimmunoradiotherapy-AT=87: 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 1675.2±2157.1 days and cumulative 5-year survival (5YS) reached 41.8%, 10 years – 35%, 20 years – 25.1%. 112 patients lived more than 5 years without progression. 216 patients died because of generalization. 5YS of upper third ECP (55.7%) was significantly superior in comparison with middle & lower third ECP (38.7%) after surgery (P=0.00175 by log-rank test). Cox modeling displayed that 5YS significantly depended on: phase transition (PT) early-invasive cancer in terms of synergetics, PT N0--N12, tumor localization, T1-4, G1-3, histology, blood cell subpopulations, age, etc. (P=0.000-0.039). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive cancer (rank=1), localization (2), healthy cells/cancer cells (CC) (3), lymphocytes/CC (4), PT N0--N12 (5), thrombocytes/CC (6), leucocytes/CC (7), erythrocytes/CC (8), AT (9). Correct prediction of 5YS was 100% by neural networks computing. CONCLUSIONS: 5YS of upper third ECP was significantly superior in comparison with middle & lower third ECP after radical procedures and strongly depended on PT early-invasive cancer, lymph node metastases, cell ratio factors and AT.
  • 3. DATA:  Males………………………………………………….320  Females………..………………………………….......108  Age=55.7±8.8 years  Tumor Size=6.6±3.3 cm  Only Surgery.………………………………………...341  Adjuvant Chemoimmunoradiotherapy (5FU+thymalin/taktivin, 5-6 cycles+RT 45-50Gy)….87
  • 4. RADICAL PROCEDURES::  Left Thoracoabdominal Esophagogastrectomies (Garlock)……………………..………………………273  Right Thoracoabdominal Esophagogastrectomies  (Ivor Lewis)………………….……………………….155  Combined Esophagogastrectomies with Resection of Diaphragm, Pericardium, Lung, Liver, Pancreas,  VCS, Aorta, Splenectomy…………………………...133  2-Field Lymphadenectomy….………………………302  3-Field Lymphadenectomy….………………………126  Upper Third…………………………………………..59  Middle Third………………………………………….50  Lower Third…………………………………………271  Total Esophagus………………………………………48
  • 5. STAGING:  T1…….66 N0..….184 G1…………118  T2……103 N1…….58 G2…………105  T3……148 N2…...186 G3…………205  T4……111 M1….….0  Adenocarcinoma…………………………….230  Squamos Cell Carcinoma…………………..188  Mix Carcinoma..……………………………...10  Early Cancer……………………………….…47  Invasive Cancer……………………………..381
  • 6. SURVIVAL RATE:  Alive………………………………………....185 (43.2%)  5-Year Survivors…………..………………..112 (26.2%)  10-Year Survivors…………………………...63 (14.7%)  Losses……………………………………….216 (50.5%)  General Life Span=1675.2±2157.1 days  For 5-Year Survivors=4490.8±2592.2 days  For 10-Year Survivors=6013±2542.9 days  For Losses=635.2±323.6 days  Cumulative 5-Year Survival………………..41.8%  Cumulative 10-Year Survival………………35%  Cumulative 20-Year Survival………………25.1%
  • 7. GENERAL ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (KAPLAN-MEIER) (N=428):
  • 8. RESULTS OF UNIVARIATE ANALYSIS OF LOCALIZATION (UPPER/3 VS. MIDDLE/3 & LOWER/3) IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):
  • 9. RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION EARLY—INVASIVE CANCER IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428)
  • 10. RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION N0—N1-2 IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):
  • 11. RESULTS OF UNIVARIATE ANALYSIS OF ADJUVANT CHEMOIMMUNORADIOTHERAPY IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):
  • 12. RESULTS OF COX REGRESSION MODELING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVALAFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=428): Cox Proportional Hazards Results Chi-square P value Localization: Upper/3 vs. Others/3 4.27775 0.038614 N0---N12 9.55416 0.001995 T1-4 43.87534 0.000000 Age 9.25605 0.002347 G1-3 27.90780 0.000000 Histology 6.87734 0.008730 Prothrombin Index 12.07929 0.000510 Adjuvant Chemoimmunoradiotherapy 17.65735 0.000026 Phase Transition Early---Invasive Cancer 5.95464 0.014679 Residual Nitrogen 15.07960 0.000103 Protein 8.73003 0.003130 Leucocytes 8.88698 0.002872 Eosinophils 9.38542 0.002187 StickP Neutrophils 9.42220 0.002144 Segmented Neutrophils 8.93026 0.002805 Lymphocytes 8.30869 0.003946 Monocytes 6.14115 0.013207
  • 13. RESULTS OF NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=328): Factor Rank Sensitivity Phase Transition Early---Invasive Cancer 1 38130 Localization 2 11348 Healthy Cells/Cancer Cells 3 7478 Lymphocytes/Cancer Cells 4 6958 Phase Transition N0---N12 5 4853 Thrombocytes/Cancer Cells 6 3260 Leucocytes/Cancer Cells 7 3196 Erythrocytes/Cancer Cells 8 3075 Adjuvant Chemoimmunoradiotherapy 9 1 Corect Classification Rate=100% Error=0.000 Area under ROC Curve=1.000
  • 14. RESULTS OF BOOTSTRAP SIMULATION IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVALAFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=328): Significant Factors (Number of Samples=3333) Rank Kendal Tau-A P T1-4 1 -0.245 0.000 Tumor Size 2 -0.239 0.000 Healthy Cells/Cancer Cells 3 0.231 0.000 Erythrocytes/Cancer Cells 4 0.224 0.000 Leucocytes/Cancer Cells 5 0.218 0.000 Lymphocytes/Cancer Cells 6 0.212 0.000 Thrombocytes/Cancer Cells 7 0.199 0.000 Segmented Neutrophils/Cancer Cells 8 0.193 0.000 Phase Transition N0---N12 9 -0.177 0.000 Eosinophils/Cancer Cells 10 0.171 0.000 Residual Nitrogen 11 -0.164 0.000 Monocytes/Cancer Cells 12 0.163 0.000 Coagulation Time 13 -0.162 0.000 Blood Chlorides 14 0.142 0.000 Phase Transition Early---Invasive Cancer 15 -0.133 0.000 G1-3 16 -0.115 0.01 Histology 17 -0.102 0.05 Stick Neutrophils/Cancer Cells 18 0.101 0.05 Tumor Growth 19 -0.093 0.05 Localization (Upper/3 vs. Others) 20 0.079 0.05
  • 15. RESULTS OF KOHONEN SELF-ORGANIZING NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=328):
  • 17. PROGNOSTIC SEPATH-MODEL OF ESOPHAGEAL CANCER PATIENTS SURVIVALAFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=328):
  • 18. 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