1. 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
Oleg Kshivets , MD, PhD
Surgery Department, Kaluga Cancer Center, Kaluga, Russia

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 (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 ± 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= 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= ). 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
T4…… 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± days
For 5-Year Survivors=4490.8± days
For 10-Year Survivors=6013± 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
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. Cox Proportional Hazards Results Chi-square P value
Results of Cox Regression Modeling in Prediction of Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=428):
Cox Proportional Hazards Results
Chi-square
P value
Localization: Upper/3 vs. Others/3
N0---N12
T1-4
Age
G1-3
Histology
Prothrombin Index
Adjuvant Chemoimmunoradiotherapy
Phase Transition Early---Invasive Cancer
Residual Nitrogen
Protein
Leucocytes
Eosinophils
StickP Neutrophils
Segmented Neutrophils
Lymphocytes
Monocytes

13. Corect Classification Rate=100% Error=0.000 Area under ROC Curve=1.000
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
Corect Classification Rate=100%
Error=0.000
Area under ROC Curve=1.000

14. Results of Bootstrap Simulation in Prediction of Esophageal Cancer Patients Survival after 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
Healthy Cells/Cancer Cells 3
0.231
Erythrocytes/Cancer Cells 4
0.224
Leucocytes/Cancer Cells 5
0.218
Lymphocytes/Cancer Cells 6
0.212
Thrombocytes/Cancer Cells 7
0.199
Segmented Neutrophils/Cancer Cells 8
0.193
Phase Transition N0---N12 9
-0.177
Eosinophils/Cancer Cells 10
0.171
Residual Nitrogen 11
-0.164
Monocytes/Cancer Cells 12
0.163
Coagulation Time 13
-0.162
Blood Chlorides 14
0.142
Phase Transition Early---Invasive Cancer 15
-0.133
G1-3 16
-0.115
0.01
Histology 17
-0.102
0.05
Stick Neutrophils/Cancer Cells 18
0.101
Tumor Growth 19
-0.093
Localization (Upper/3 vs. Others) 20
0.079

15. Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=328):

16. Esophageal Cancer Dynamics:

17. Prognostic SEPATH-Model of Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=328):

18. Address: oleg Kshivets M. D. , Ph. D
Address: oleg Kshivets M.D., Ph.D., Consultant Thoracic, Abdominal, General Surgeon & Surgical Oncologist
skype: okshivets
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