PRECISE PREDICTION OF PRECISE PREDICTION OF 5-YEAR SURVIVAL OF ESOPHAGEAL AND 5-YEAR SURVIVAL OF ESOPHAGEAL AND CARDIOESOPHAGEAL CANCER PATIENTS CARDIOESOPHAGEAL CANCER PATIENTS AFTER ESOPHAGOGASTRECTOMIES AFTER ESOPHAGOGASTRECTOMIES Oleg Kshivets , MD, PhD Oleg Kshivets , MD, PhD
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PRECISE PREDICTION OF PRECISE PREDICTION OF 5-YEAR SURVIVAL OF ESOPHAGEAL 5-YEAR SURVIVAL OF ESOPHAGEAL AND CARDIOESOPHAGEAL CANCER AND CARDIOESOPHAGEAL CANCER
PATIENTS AFTER PATIENTS AFTER ESOPHAGOGASTRECTOMIESESOPHAGOGASTRECTOMIES
Oleg Kshivets , MD, PhDOleg Kshivets , MD, PhD
Abstract: PRECISE PREDICTION OF 5-YEAR SURVIVAL OF ESOPHAGEAL AND CARDIOESOPHAGEAL CANCER PATIENTS AFTER ESOPHAGOGASTRECTOMIES Oleg Kshivets OBJECTIVE: We examined factors in terms of precise prediction of 5-year survival (5YS) of esophageal and cardioesophageal cancer (ECEC) patients (ECECP) (T1-4N0M1A) after complete (R0) esophagogastrectomies (EG). METHODS: We analyzed data of 407 consecutive ECECP (age=55.6±8.6 years; tumor size=6.7±3.3 cm) radically operated and monitored in 1975-2011 (m=305, f=102;EG Garlock=271, EG Lewis=136, combined EG with resection of pancreas, liver, diaphragm, colon transversum, lung, trachea, pericardium, splenectomy=125; adenocarcinoma=212, squamous=185, mix=10; T1=62, T2=96, T3=140, T4=109; N0=167, N1=56, M1A=184, G1=116, G2=96, G3=195; early ECEC=43, invasive=364). 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 1612.6±2070.5 days and cumulative 5-year survival (5YS) reached 40%, 10 years – 32.7%, 20 years – 23.5%. 101 ECECP lived more than 5 years without cancer. 215 ECECP died because of ECEC. Cox modeling displayed (Chi2=232, df=26, P=0.000) that 5YS of ECECP significantly depended on: phase transition (PT) N0—N1-M1A in terms of synergetics, cell ratio factors (CRF) (ratio between cancer cells and blood cells subpopulations), T, G, tumor growth, tumor size, sex, age, adjuvant chemotherapy, localization, blood cells, prothrombin index, ESS, blood chlorides, residual nitrogen (P=0.000-0.043). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT N0--N1-M1A (rank=1), PT early-invasive ECEC (rank=2), tumor size, prothrombin index, blood cells, ESS, age, CRF, blood chlorides, residual nitrogen, localization, adjuvant chemotherapy. Correct prediction of 5YS was 100% by neural networks computing. CONCLUSIONS: 5YS of ECECP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N1-M1A; 3) CRF; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) anthropometric data; 8) adjuvant chemotherapy; 9) tumor localization.
• Age=5Age=555..66±±88..66 years years• Tumor Size=Tumor Size=66..77±±33..33 cm cm• Only Surgery.……………………………………Only Surgery.………………………………………...324…...324• Adjuvant ChemoimmunoAdjuvant Chemoimmunoradio/Chemoimmunotherapyradio/Chemoimmunotherapy
Radical Procedures:Radical Procedures:• Left Thoracoabdominal Esophagogastrectomies Left Thoracoabdominal Esophagogastrectomies
(Garlock)……………………..………………271(Garlock)……………………..………………271• Right Thoracoabdominal Esophagogastrectomies Right Thoracoabdominal Esophagogastrectomies • (Ivor Lewis)………………….………………136(Ivor Lewis)………………….………………136• Combined Esophagogastrectomies with Combined Esophagogastrectomies with • Resection of Diaphragm, Pericardium, Lung, Resection of Diaphragm, Pericardium, Lung,
Right Thoracoabdominal Esophagogastrectomy Right Thoracoabdominal Esophagogastrectomy (Ivor Lewis)......................................................136(Ivor Lewis)......................................................136
Ivor Lewis Procedures…………………136Ivor Lewis Procedures…………………136
Survival Rate:Survival Rate:• Alive………………………………………....167 (41%)Alive………………………………………....167 (41%)• 5-Year Survivors…………..……………….101 (24.8%) 5-Year Survivors…………..……………….101 (24.8%) • 10-Year Survivors…………………………...53 (13%)10-Year Survivors…………………………...53 (13%)• Losses………………………………………215 (52.8%)Losses………………………………………215 (52.8%)• General Life Span=1612.6General Life Span=1612.6±2070.5 days±2070.5 days• For 5-Year Survivors=4404.4±2543.9 daysFor 5-Year Survivors=4404.4±2543.9 days• For 10-Year Survivors=6095.9±2468.3 daysFor 10-Year Survivors=6095.9±2468.3 days• For Losses=691.1±389.5 daysFor Losses=691.1±389.5 days• Cumulative 5-Year Survival………………..40%Cumulative 5-Year Survival………………..40%• Cumulative 10-Year Survival………………32.7%Cumulative 10-Year Survival………………32.7%
General General EEsophagealsophageal/Cardioesophageal/Cardioesophageal Cancer Patients Survival Cancer Patients Survival after Complete Esophagogastrectomies (Kaplan-Meier) (after Complete Esophagogastrectomies (Kaplan-Meier) (n=n=407)407)
Survival FunctionGeneral Esophageal and Cardioesophageal Cancer Patients Survival after
Results of Univariate Analysis Results of Univariate Analysis of Phase Transition Early—Invasive of Phase Transition Early—Invasive Cancer iCancer in Prediction of n Prediction of EEsophagealsophageal/Cardioesophageal/Cardioesophageal Cancer Cancer
Cumulative Proportion Surviving (Kaplan-Meier)Cumulative 5-Year Survival of Early Cancer Patients=100%
Cumulative 5-Year Survival of Invasive Cancer Patients=33.2%P=0.000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
-0.2
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0.4
0.6
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1.0
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Invasive Cancer Patients=364 Early Cancer Patients=43
Results of Univariate Analysis Results of Univariate Analysis of Phase Transition N0—N1M1A of Phase Transition N0—N1M1A in in Prediction of Prediction of EEsophagealsophageal/Cardioesophageal/Cardioesophageal Cancer Patients Cancer Patients
SurvivalSurvival ( (n=n=407)407)
Cumulative Proportion Surviving (Kaplan-Meier)Cumulative 5-Year Survival of Cancer Patients with N0=60.3%
Cumulative 5-Year Survival of Cancer Patients with N1-M1A=25.1%P=0.000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.0
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Cancer Patients with N0=167 Cancer Patients with N1-M1A=240
Results of Univariate Analysis Results of Univariate Analysis of Adjuvant Therapy of Adjuvant Therapy in Prediction of in Prediction of EEsophagealsophageal/Cardioesophageal /Cardioesophageal Cancer Patients Survival Cancer Patients Survival ( (n=n=407)407)
5-Year Survival after Adjuvant Treatment=60.8%;5-Year Survival after Surgery Along=36.4%;
P=0.00018 by Log-Rank Test
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
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Adjuvant Treatment, n=83 Only Surgery, n=324
Results of Univariate Analysis Results of Univariate Analysis of Tumor Localization of Tumor Localization in Prediction in Prediction of of EEsophagealsophageal/Cardioesophageal /Cardioesophageal Cancer Patients Survival Cancer Patients Survival ( (n=n=407)407)
5-Year Survival of Esophageal Cancer Patients=49.1%;5-Year Survival of Cardioesophageal Cancer Patients=34.4%;
P=0.003 by Log-Rank Test
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.0
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Cardioesophageal Cancer Patients, n=272 Esophageal Cancer Patients, n=135
Results of Cox Regression Modeling in Prediction of Results of Cox Regression Modeling in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophageal/Cardioesophageal Cancer Patients Survival after Complete
Results of Neural Networks ComputingResults of Neural Networks Computing in Prediction of in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophageal/Cardioesophageal Cancer Patients Survival after Complete
Results of Bootstrap Simulation Results of Bootstrap Simulation in Prediction of Esophageal Cancer in Prediction of Esophageal Cancer Patients Survival after Complete Esophagectomies (n=316Patients Survival after Complete Esophagectomies (n=316))
Holling-Tenner Models of Esophageal /Cardioesophageal Cancer Holling-Tenner Models of Esophageal /Cardioesophageal Cancer Cell Population and Cytotoxic Cell Population DynamicsCell Population and Cytotoxic Cell Population Dynamics
Results of Results of Kohonen Self-Organizing Kohonen Self-Organizing Neural Neural Networks Computing in Prediction ofNetworks Computing in Prediction of
Esophageal/Cardioesophageal CEsophageal/Cardioesophageal Cancer Patients ancer Patients SurvivalSurvival after Complete Esophagogastrectomies after Complete Esophagogastrectomies
(n=316) (n=316)
Esophageal/Cardioesophageal Cancer DynamicsEsophageal/Cardioesophageal Cancer Dynamics
Prognostic SEPATH-Model of Esophageal/Cardioesophageal Prognostic SEPATH-Model of Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophagectomies, n=316Cancer Patients Survival after Complete Esophagectomies, n=316
Conclusions:Conclusions:• 5-Year Survival of Esophageal and Cardioesophageal 5-Year Survival of Esophageal and Cardioesophageal
Cancer Patients after Radical Procedures Cancer Patients after Radical Procedures Significantly Depended on: Significantly Depended on:
• 1) Phase Transition “Early—Invasive Cancer”; 1) Phase Transition “Early—Invasive Cancer”; • 2) Phase Transition N0—N1M1A; 2) Phase Transition N0—N1M1A; • 3) Cell Ratio Factors (ratio between cancer cells and 3) Cell Ratio Factors (ratio between cancer cells and