Kshivets IASLC_Vienna2016

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Transcript of Kshivets IASLC_Vienna2016

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5-Year Survival of Lung Cancer Patients after Radical Surgery was Significantly Depended on Tumor Characteristics, Blood Cell Circuit, Cell Ratio Factors, Hemostasis System and Adjuvant Treatment

Oleg Kshivets, MD, PhD Surgery Department, Khimki Clinic N1, Moscow, Russia 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 676 consecutive LCP (age=57.58.3 years; tumor size=4.42.4 cm) radically operated and monitored in 1985-2016 (m=585, f=91; lobectomies=431, pneumonectomies=245, mediastinal lymph node dissection=676; combined LP with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=188; only surgery-S=532, adjuvant chemoimmunoradiotherapy-AT=144: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=239, T2=249, T3=131, T4=57; N0=428, N1=130, N2=118, M0=676; G1=168, G2=202, G3=306; squamous=381, adenocarcinoma=249, large cell=46; early LC=134, invasive LC=542. 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 2109.11692.4 days (median=1936 days) and cumulative 5-year survival (5YS) reached 69.7%, 10 years 61.4%, 20 years 42.9%. 419 LCP lived more than 5 years without cancer, 111 10 years, 14 20 years. 195 LCP died because of LC (LS=560372.1 days). AT significantly improved 5YS (64.4% vs. 34.1%) (P=0.00002 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0-N12, histology, G, blood cell circuit, cell ratio factors (ratio between blood cells subpopulations and cancer cells-CC), prothrombin index, heparin tolerance, recalcification time, glucose, AT (P=0.000-0.041). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT N0-N12 (rank=1), PT early-invasive LC (rank=2), eosinophils/CC (3), prothrombin index (4), thrombocytes/CC (5), glucose (6),lymphocytes/CC (7), erythrocytes/CC (8), healthy cells/CC (9), segmented neutrophils/CC (10), stick neutrophils/CC (11), monocytes/CC (12), leucocytes/CC (13). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0). CONCLUSIONS: 5-year survival of lung cancer patients after radical procedures significantly depended on: 1) phase transition early-invasive lung cancer; 2) phase transition N0--N12; 3) tumor characteristics; 4) blood cell circuit; 5) cell ratio factors; 6) hemostasis system; 7) biochemical homeostasis; 8) surgery type; 9) adjuvant chemoimmunoradiotherapy; 10) anthropometric data.

Cox RegressionParameterEstimateStandardErrorChi-squareP value95% Lower CL95% Upper CLHazardRatioHistology0.278030.08755110.084670.0014950.106430.4496271.320526G0.341280.08947714.547820.0001370.165910.5166491.406744Glucose-0.289240.07914613.355410.000258-0.44436-0.1341160.748833Prothrombin Index0.031560.00675521.833230.0000030.018320.0448031.032067Recalcification Time-0.005810.00177710.708760.001066-0.00930-0.0023320.994203Heparin Tolerance0.003670.00067529.528330.0000000.002340.0049901.003674PT Early-Invasive LC-1.261230.39215810.343440.001299-2.02985-0.4926130.283305Adjuvant Chemoimmunoradiotherapy-0.940240.19434423.406320.000001-1.32114-0.5593300.390535Stick Neutrophils (tot)0.115160.0460406.256430.0123740.024920.2053981.122053PT N0--N121.085760.14709254.486540.0000000.797471.3740592.961699Eosinophils/CC-1.168980.4354217.207670.007259-2.02239-0.3155700.310684Lymphocytes/CC-0.196820.0680348.368910.003817-0.33016-0.0634720.821342Monocytes (%)-0.052230.0255354.183660.040815-0.10228-0.0021820.949111

Neural Networks: n=614 Baseline Error=0.000; Area under ROC Curve=1.000; Correct Classification Rate=100% Rank Sensitivity PT N0---N12 1 6079 PT Early---Invasive Cancer2 5728 Eosinophils/Cancer Cells3 2324 Prothrombin Index4 2205 Thrombocytes/Cancer Cells5 1712 Glucose6 1644 Lymphocytes/Cancer Cells7 1598 Erythrocytes/Cancer Cells 8 1370 Healthy Cells/Cancer Cells9 1188 Segmented Neutrophils/Cancer Cells10 1185 Stick Neutrophils/Cancer Cells11939Monocytes/Cancer Cells 12 929 Leucocytes/Cancer Cells 13 487

Bootstrap SimulationRankKendallTau-AP