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Kshivets milan2014

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Oleg Kshivets , MD, PhDSurgery Department, Kaluga Cancer Center, Kaluga, Russia5-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

ABSTRACT5-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=55.78.8 years; tumor size=6.63.3 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 1675.22157.1 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.320Females.........108

Age=55.78.8 yearsTumor Size=6.63.3 cmOnly Surgery....341Adjuvant Chemoimmunoradiotherapy (5FU+thymalin/taktivin, 5-6 cycles+RT 45-50Gy).87

Radical Procedures::Left Thoracoabdominal Esophagogastrectomies (Garlock)..273Right Thoracoabdominal Esophagogastrectomies (Ivor Lewis)..155Combined Esophagogastrectomies with Resection of Diaphragm, Pericardium, Lung, Liver, Pancreas, VCS, Aorta, Splenectomy...1332-Field Lymphadenectomy.3023-Field Lymphadenectomy.126Upper Third..59Middle Third.50Lower Third271Total Esophagus48

Staging:T1.66 N0...184 G1118T2103 N1.58 G2105T3148 N2...186 G3205T4111 M1..0Adenocarcinoma.230 Squamos Cell Carcinoma..188 Mix Carcinoma.....10Early Cancer.47Invasive Cancer..381

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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=1675.22157.1 daysFor 5-Year Survivors=4490.82592.2 daysFor 10-Year Survivors=60132542.9 daysFor Losses=635.2323.6 daysCumulative 5-Year Survival..41.8%Cumulative 10-Year Survival35%Cumulative 20-Year Survival25.1%

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 EarlyInvasive Cancer in Prediction of Esophageal Cancer Patients Survival (n=428)

Results of Univariate Analysis of Phase Transition N0N1-2 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 Survival after Complete Esophagogastrectomies (n=428):

Cox Proportional Hazards Results Chi-squareP valueLocalization: Upper/3 vs. Others/3 4.277750.038614N0---N129.554160.001995T1-443.875340.000000Age9.256050.002347G1-327.907800.000000Histology6.877340.008730Prothrombin Index12.079290.000510Adjuvant Chemoimmunoradiotherapy17.657350.000026Phase Transition Early---Invasive Cancer5.954640.014679Residual Nitrogen15.079600.000103Protein8.730030.003130Leucocytes8.886980.002872Eosinophils9.385420.002187StickP Neutrophils9.422200.002144Segmented Neutrophils8.930260.002805Lymphocytes8.308690.003946Monocytes6.141150.013207

Results of Neural Networks Computing in Prediction of Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=328):

FactorRankSensitivityPhase Transition Early---Invasive Cancer138130Localization211348Healthy Cells/Cancer Cells37478Lymphocytes/Cancer Cells46958Phase Transition N0---N1254853Thrombocytes/Cancer Cells63260Leucocytes/Cancer Cells73196Erythrocytes/Cancer Cells83075Adjuvant Chemoimmunoradiotherapy91

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

Results of Bootstrap Simulation in Prediction of Esophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=328):

Significant Factors (Number of Samples=3333)RankKendal Tau-APT1-41-0.2450.000Tumor Size2-0.2390.000Healthy Cells/Cancer Cells30.2310.000Erythrocytes/Cancer Cells40.2240.000Leucocytes/Cancer Cells50.2180.000Lymphocytes/Cancer Cells60.2120.000Thrombocytes/Cancer Cells70.1990.000Segmented Neutrophils/Cancer Cells80.1930.000Phase Transition N0---N129-0.1770.000Eosinophils/Cancer Cells100.1710.000Residual Nitrogen11-0.1640.000Monocytes/Cancer Cells120.1630.000Coagulation Time13-0.1620.000Blood Chlorides140.1420.000Phase Transition Early---Invasive Cancer15-0.1330.000G1-316-0.1150.01Histology17-0.1020.05Stick Neutrophils/Cancer Cells180.1010.05Tumor Growth19-0.0930.05Localization (Upper/3 vs. Others)200.0790.05

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

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Esophageal Cancer Dynamics:

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

Address:oleg KshivetsM.D., Ph.D.,

Consultant Thoracic, Abdominal, General Surgeon & Surgical Oncologist

e-mail: [email protected] skype: okshivets http: //www.ctsnet.org/home/okshivets

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