Kshivets iaslc denver2015

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Oleg Kshivets , MD, PhDSurgery Department, Kaluga Cancer Clinical Center, RussiaPRECISE PREDICTION OF 5-YEAR SURVIVAL OF LUNG CANCER PATIENTS AFTER RADICAL SURGERY

ABSTRACTPrecise Prediction of 5-Year Survival of Lung Cancer Patients after Radical SurgeryOleg Kshivets OBJECTIVE: This study aimed to determine homeostasis and tumor factors for 5-year survival (5YS) of non-small cell lung cancer (LC) patients (LCP) (T1-4N0-2M0) after complete en block (R0) lobectomies/pneumonectomies (LP). METHODS: We analyzed data of 665 consecutive LCP (age=57.58.3 years; tumor size=4.42.4 cm) radically operated and monitored in 1985-2015 (m=575, f=90; lobectomies=423, pneumonectomies=242, combined LP with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=180; only surgery-S=524, adjuvant chemoimmunoradiotherapy-AT=141: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=237, T2=248, T3=125, T4=55; N0=419, N1=130, N2=116, M0=665; G1=163, G2=199, G3=303; squamous=377, adenocarcinoma=243, large cell=45; early LC=132, invasive LC=533. 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 2114.81685 days and cumulative 5YS reached 69.6%, 10 years 61.2%, 20 years 43.1%. 416 LCP lived more than 5 years without cancer (LS=3041.41472.5 days). 193 LCP died because of LC (LS=559.6373.5 days). AT significantly improved 5YS (65.1% vs. 34.3%) (P=0.00001 by log-rank test) only for LCP with N1-2. Cox modeling displayed (Chi2=290.78, df=13, P=0.000) that 5YS of LCP significantly depended on: phase transition (PT)early-invasive LC, PT N0-N12, histology, G, blood cell subpopulations, cell ratio factors (ratio between blood cells subpopulations and cancer cells-CC), prothrombin index, heparin tolerance, recalcification time, glucose, AT (P=0.000-0.035). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT N0-N12 (rank=1), PT early-invasive LC (rank=2), lymphocytes (3), segmented neutrophils (4), tumor size (5), AT (6), T1-4 (7), ESS (8), prothrombin index (9), glucose (10), thrombocytes/CC (11), healthy cells/CC (12), lymphocytes/CC (13), erythrocytes/CC (14). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0). CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: tumor characteristics, blood cell circuit, cell ratio factors, hemostasis system and AT.

Data:Males.575Females...........90

Age=57.58.3 yearsTumor Size=4.42.4 cmOnly Surgery....524Adjuvant Chemoimmunoradiotherapy (CAV/gemzar+ cisplatin+thymalin/taktivin, 5-6 cycles+ Radiotherapy 45-50Gy)...141

Radical Procedures::Pneumonectomies (R0).....242Lobectomies (R0)..423Combined Pneumonectomies/Lobectomies with Resection of Trachea, Carina, Atrium, Aorta, Vena Cava Superior, Vena Azygos, Diaphragm, Pericardium, Esophagus, Liver, Ribs (R0)....180N1 Lymph Node Dissection..132Mediastinal Lymph Node Dissection...533

Staging:T1237 N0...419 G1163T2248 N1...130 G2199T3125 N2...116 G3303T4..55 M0..665Adenocarcinoma.243 Squamos Cell Carcinoma...377 Large Cell Carcinoma..45Early Cancer132Invasive Cancer...533

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Survival Rate:Alive....434 (65.3%)5-Year Survivors.....416 (62.6%) 10-Year Survivors...108 (16.2%)Losses..193 (29%)General Life Span=2114.81685 daysFor 5-Year Survivors=3041.41472.5 daysFor 10-Year Survivors=5053.81477.2 daysFor Losses=559.6373.5 daysCumulative 5-Year Survival..69.6%Cumulative 10-Year Survival61.2%Cumulative 20-Year Survival43.1%

General Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (Kaplan-Meier) (n=665):

Results of Univariate Analysis of Phase Transition EarlyInvasive Cancer in Prediction of Lung Cancer Patients Survival (n=665)

Results of Univariate Analysis of Phase Transition N0N1-2 in Prediction of Lung Cancer Patients Survival (n=665):

Results of Univariate Analysis of Adjuvant chemoimmunoradioTherapy in Prediction of Lung Cancer Patients Survival with N1-2 (n=246):

Results of Cox Regression Modeling in Prediction of Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (n=665):

Cox Proportional Hazard Results: Chi = 290.777 df = 13 p = 0.0000; n=665 Factors:Parameter EstimateStandard ErrorChiP95% Lower CL95% Upper CLHazard Ratio95% Hazard Ratio Lower CL95% Hazard Ratio Upper CL Histology0.287290.08815010.621400.0011180.114510.4600581.3328061.1213291.584165 G1-30.334160.09019413.726390.0002110.157380.5109391.3967691.1704451.666855 Phase Transition Early-Invasive Cancer-1.300810.39354010.925670.000948-2.07213-0.5294830.2723120.1259170.588909 Adjuvant Chemoimmunoradiotherapy-1.001230.20124324.752930.000001-1.39566-0.6068030.3674260.2476690.545091 Phase Transition N0---N121.070940.14880551.795280.0000000.779281.3625882.9181082.1799083.906291 Glucose-0.284640.08133812.246330.000466-0.44406-0.1252210.7522850.6414270.882302 Prothrombin Index0.030350.00684719.653020.0000090.016930.0437731.0308191.0170781.044746 Recalcification Time-0.005990.00178611.244860.000798-0.00949-0.0024880.9940300.9905570.997515 Heparin Tolerance0.003660.00066929.848590.0000000.002340.0049671.0036621.0023471.004979 Eosinophils/Cancer Cells-1.016500.4303095.580240.018164-1.85989-0.1731080.3618600.1556900.841046 Lymphocytes/Cancer Cells-0.178370.0676746.947060.008396-0.31101-0.0457320.8366330.7327070.955298 Erythrocytes tot-0.037760.0179294.434980.035210-0.07290-0.0026170.9629470.9296960.997386 Thrombocytes tot0.000490.0001926.458380.0110430.000110.0008631.0004871.0001111.000863

Results of Neural Networks Computing in Prediction of Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (n=609):

FactorRankSensitivityPhase Transition N0---N1214552Phase Transition Early---Invasive Cancer22430Lymphocytes32182Segmented Neutrophils42109Tumor Size51551Adjuvant Chemoimmunoradiotherapy61483T1-471478ESS81209Prothrombin Index91107Glucose10999Thrombocytes/Cancer Cells11906Healthy Cells/Cancer Cells12624Lymphocytes/Cancer Cells13509Erythrocytes/Cancer Cells14404

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

Results of Bootstrap Simulation in Prediction of Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (n=609): Significant Factors (Number of Samples=3333)RankKendal Tau-AP Phase Transition N0---N121-0.2150.000 Lymphocytes/Cancer Cells2-0.2060.000 Healthy Cells/Cancer Cells3-0.2030.000 Erythrocytes/Cancer Cells4-0.2020.000 Thrombocytes/Cancer Cells5-0.1760.000 Leucocytes/Cancer Cells6-0.1680.000 Prothrombin Index70.1620.000 Tumor Size8-0.1440.000 Eosinophils/Cancer Cells9-0.1400.000 Phase Transition Early---Invasive Cancer10-0.1310.000 T1-4110.1260.000 Monocytes/Cancer Cells12-0.1250.000 Segmented Neutrophils/Cancer Cells13-0.1150.000 Segmented Neutrophils140.1070.000 Weight15-0.1040.000 Lymphocytes16-0.1020.000 Erythrocytes17-0.0980.001 ESS180.0840.01 G1-319-0.0820.01 Heparin Tolerance 200.0770.01 Glucose21-0.0710.01 Surgery alone 22-0.0660.01 Eosinophils23-0.0620.05

Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (n=609):

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Lung Cancer Dynamics:

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Prognostic SEPATH-Model of Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (n=609):

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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