1
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
