kshivets milan2014

18
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

Upload: oleg-kshivets

Post on 22-Aug-2014

1.148 views

Category:

Health & Medicine


0 download

DESCRIPTION

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

TRANSCRIPT

Page 1: Kshivets milan2014

Oleg Kshivets , MD, PhDSurgery 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

Page 2: Kshivets milan2014

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=55.7±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.

Page 3: Kshivets milan2014

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

Page 4: Kshivets milan2014

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

Page 5: Kshivets milan2014

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

Page 6: Kshivets milan2014

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%

Page 7: Kshivets milan2014

GENERAL ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES(KAPLAN-MEIER) (N=428):

Page 8: Kshivets milan2014

RESULTS OF UNIVARIATE ANALYSIS OF LOCALIZATION (UPPER/3 VS. MIDDLE/3 & LOWER/3) IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):

Page 9: Kshivets milan2014

RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION EARLY—INVASIVE CANCER IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428)

Page 10: Kshivets milan2014

RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION N0—N1-2 IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):

Page 11: Kshivets milan2014

RESULTS OF UNIVARIATE ANALYSIS OF ADJUVANT CHEMOIMMUNORADIOTHERAPY IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL (N=428):

Page 12: Kshivets milan2014

RESULTS OF COX REGRESSION MODELING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE

ESOPHAGOGASTRECTOMIES (N=428):

Cox Proportional Hazards Results Chi-square P valueLocalization: Upper/3 vs. Others/3 4.27775 0.038614N0---N12 9.55416 0.001995T1-4 43.87534 0.000000Age 9.25605 0.002347G1-3 27.90780 0.000000Histology 6.87734 0.008730Prothrombin Index 12.07929 0.000510Adjuvant Chemoimmunoradiotherapy 17.65735 0.000026Phase Transition Early---Invasive Cancer 5.95464 0.014679Residual Nitrogen 15.07960 0.000103Protein 8.73003 0.003130Leucocytes 8.88698 0.002872Eosinophils 9.38542 0.002187StickP Neutrophils 9.42220 0.002144Segmented Neutrophils 8.93026 0.002805Lymphocytes 8.30869 0.003946Monocytes 6.14115 0.013207

Page 13: Kshivets milan2014

RESULTS OF NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=328):

Factor Rank SensitivityPhase Transition Early---Invasive Cancer 1 38130Localization 2 11348Healthy Cells/Cancer Cells 3 7478Lymphocytes/Cancer Cells 4 6958Phase Transition N0---N12 5 4853Thrombocytes/Cancer Cells 6 3260Leucocytes/Cancer Cells 7 3196Erythrocytes/Cancer Cells 8 3075Adjuvant Chemoimmunoradiotherapy 9 1

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

Page 14: Kshivets milan2014

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 PT1-4 1 -0.245 0.000Tumor Size 2 -0.239 0.000Healthy Cells/Cancer Cells 3 0.231 0.000Erythrocytes/Cancer Cells 4 0.224 0.000Leucocytes/Cancer Cells 5 0.218 0.000Lymphocytes/Cancer Cells 6 0.212 0.000Thrombocytes/Cancer Cells 7 0.199 0.000Segmented Neutrophils/Cancer Cells 8 0.193 0.000Phase Transition N0---N12 9 -0.177 0.000Eosinophils/Cancer Cells 10 0.171 0.000Residual Nitrogen 11 -0.164 0.000Monocytes/Cancer Cells 12 0.163 0.000Coagulation Time 13 -0.162 0.000Blood Chlorides 14 0.142 0.000Phase Transition Early---Invasive Cancer 15 -0.133 0.000G1-3 16 -0.115 0.01Histology 17 -0.102 0.05Stick Neutrophils/Cancer Cells 18 0.101 0.05Tumor Growth 19 -0.093 0.05Localization (Upper/3 vs. Others) 20 0.079 0.05

Page 15: Kshivets milan2014

RESULTS OF KOHONEN SELF-ORGANIZING NEURAL NETWORKS COMPUTING IN PREDICTION OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE ESOPHAGOGASTRECTOMIES (N=328):

Page 16: Kshivets milan2014

ESOPHAGEAL CANCER DYNAMICS:

Page 17: Kshivets milan2014

PROGNOSTIC SEPATH-MODEL OF ESOPHAGEAL CANCER PATIENTS SURVIVAL AFTER COMPLETE

ESOPHAGOGASTRECTOMIES (N=328):

Page 18: Kshivets milan2014

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