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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=57.5±8.3 years; tumor size=4.4±2.4 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 2109.1±1692.4 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=560±372.1 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 Regression Parameter
Estimate
Standard
Error
Chi-square P value 95% Lower CL 95% Upper CL Hazard
Ratio
Histology 0.27803 0.087551 10.08467 0.001495 0.10643 0.449627 1.320526
G 0.34128 0.089477 14.54782 0.000137 0.16591 0.516649 1.406744
Glucose -0.28924 0.079146 13.35541 0.000258 -0.44436 -0.134116 0.748833
Prothrombin Index 0.03156 0.006755 21.83323 0.000003 0.01832 0.044803 1.032067
Recalcification Time -0.00581 0.001777 10.70876 0.001066 -0.00930 -0.002332 0.994203
Heparin Tolerance 0.00367 0.000675 29.52833 0.000000 0.00234 0.004990 1.003674
PT Early-Invasive LC -1.26123 0.392158 10.34344 0.001299 -2.02985 -0.492613 0.283305
Adjuvant Chemoimmunoradiotherapy -0.94024 0.194344 23.40632 0.000001 -1.32114 -0.559330 0.390535
Stick Neutrophils (tot) 0.11516 0.046040 6.25643 0.012374 0.02492 0.205398 1.122053
PT N0--N12 1.08576 0.147092 54.48654 0.000000 0.79747 1.374059 2.961699
Eosinophils/CC -1.16898 0.435421 7.20767 0.007259 -2.02239 -0.315570 0.310684
Lymphocytes/CC -0.19682 0.068034 8.36891 0.003817 -0.33016 -0.063472 0.821342
Monocytes (%) -0.05223 0.025535 4.18366 0.040815 -0.10228 -0.002182 0.949111
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 Cancer 2 5728
Eosinophils/Cancer Cells 3 2324
Prothrombin Index 4 2205
Thrombocytes/Cancer Cells 5 1712
Glucose 6 1644
Lymphocytes/Cancer Cells 7 1598
Erythrocytes/Cancer Cells 8 1370
Healthy Cells/Cancer Cells 9 1188
Segmented Neutrophils/Cancer Cells 10 1185
Stick Neutrophils/Cancer Cells 11 939
Monocytes/Cancer Cells 12 929
Leucocytes/Cancer Cells 13 487
Bootstrap Simulation Rank Kendall’Tau-A P<
Lymphocytes/Cancer Cells 1 -0.227 0.000
Healthy Cells/Cancer Cells 2 -0.223 0.000
Erythrocytes/Cancer Cells 3 -0.221 0.000
PT N0---N12 4 0.199 0.000
Thrombocytes/Cancer Cells 5 -0.197 0.000
Leucocytes/Cancer Cells 6 -0.188 0.000
Prothrombin Index 7 0.163 0.000
Eosinophils/Cancer Cells 8 -0.161 0.000
Monocytes/Cancer Cells 9 -0.144 0.000
Tumor Size 10 0.143 0.000
Segmented Neutrophils/Cancer Cells 11 -0.134 0.000
PT Early---Invasive Cancer 12 -0.130 0.000
T1-4 13 0.126 0.000
Erythrocytes (tot) 14 -0.117 0.000
Segmented Neutrophils (%) 15 0.110 0.000
Lymphocytes (tot) 16 -0.108 0.000
Weight 17 -0.103 0.001
Lymphocytes (%) 18 -0.087 0.01
Eosinophils (tot) 19 -0.085 0.01
G1-3 20 0.083 0.01
Lymphocytes (abs) 21 -0.082 0.01
ESS 22 0.081 0.01
Heparin Tolerance 23 0.080 0.01
Stick Neutrophils/Cancer Cells 24 -0.077 0.01
Glucose 25 -0.071 0.01
Eosinophils (%) 26 -0.065 0.05
Only Surgery 27 -0.064 0.05
Eosinophils (abs) 28 -0.061 0.05
0 5 10
15
20
25
30
35
Lymphocytes/Cancer Cells
11.11.21.31.41.51.61.71.81.9
PT Early--Invasive Cancer
1
1
1.1
1.1
1.2
1.2
1.3
1.3
1.4
1.4
1.5
1.5
1.6
1.6
1.7
1.7
1.8
1.8
1.9
1.9
2
2
5-YearSurvival
5-YearSurvival
P=0.0000
z=a+blnx+cy+d(lnx)^2+ey^2+fylnx+g(lnx)^3+hy^3+iy^2lnx+jy(lnx)^2
r^2=0.15389193 DF Adj r^2=0.13979013 FitStdErr=0.43174167 Fstat=12.145684
a=1.6730247 b=0.10714131 c=-1.559062 d=-0.054738649 e=2.0848282
f=-0.42449195 g=0.0015228759 h=-0.73551088 i=0.18814164 j=0.022282855
0 5 10 15 20 25 30 35
Lymphocytes/Cancer Cells
00.10.20.30.40.50.60.70.80.9
PT N0---N12
1
1
1.1
1.1
1.2
1.2
1.3
1.3
1.4
1.4
1.5
1.5
1.6
1.6
1.7
1.7
1.8
1.8
1.9
1.9
2
2
5-YearSurvival
5-YearSurvival
P=0.0000
z=a+b/x+c/x^2+d/x^3+e/x^4+f/x^5+gy
r^2=0.24088672 DF Adj r^2=0.23207446 FitStdErr=0.40792762 Fstat=31.944196
a=0.85682428 b=1.0401408 c=-1.0202475 d=0.47891711
e=-0.098874149 f=0.0071729116 g=0.37035265

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Kshivets IASLC_Vienna2016

  • 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=57.5±8.3 years; tumor size=4.4±2.4 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 2109.1±1692.4 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=560±372.1 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 Regression Parameter Estimate Standard Error Chi-square P value 95% Lower CL 95% Upper CL Hazard Ratio Histology 0.27803 0.087551 10.08467 0.001495 0.10643 0.449627 1.320526 G 0.34128 0.089477 14.54782 0.000137 0.16591 0.516649 1.406744 Glucose -0.28924 0.079146 13.35541 0.000258 -0.44436 -0.134116 0.748833 Prothrombin Index 0.03156 0.006755 21.83323 0.000003 0.01832 0.044803 1.032067 Recalcification Time -0.00581 0.001777 10.70876 0.001066 -0.00930 -0.002332 0.994203 Heparin Tolerance 0.00367 0.000675 29.52833 0.000000 0.00234 0.004990 1.003674 PT Early-Invasive LC -1.26123 0.392158 10.34344 0.001299 -2.02985 -0.492613 0.283305 Adjuvant Chemoimmunoradiotherapy -0.94024 0.194344 23.40632 0.000001 -1.32114 -0.559330 0.390535 Stick Neutrophils (tot) 0.11516 0.046040 6.25643 0.012374 0.02492 0.205398 1.122053 PT N0--N12 1.08576 0.147092 54.48654 0.000000 0.79747 1.374059 2.961699 Eosinophils/CC -1.16898 0.435421 7.20767 0.007259 -2.02239 -0.315570 0.310684 Lymphocytes/CC -0.19682 0.068034 8.36891 0.003817 -0.33016 -0.063472 0.821342 Monocytes (%) -0.05223 0.025535 4.18366 0.040815 -0.10228 -0.002182 0.949111 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 Cancer 2 5728 Eosinophils/Cancer Cells 3 2324 Prothrombin Index 4 2205 Thrombocytes/Cancer Cells 5 1712 Glucose 6 1644 Lymphocytes/Cancer Cells 7 1598 Erythrocytes/Cancer Cells 8 1370 Healthy Cells/Cancer Cells 9 1188 Segmented Neutrophils/Cancer Cells 10 1185 Stick Neutrophils/Cancer Cells 11 939 Monocytes/Cancer Cells 12 929 Leucocytes/Cancer Cells 13 487 Bootstrap Simulation Rank Kendall’Tau-A P< Lymphocytes/Cancer Cells 1 -0.227 0.000 Healthy Cells/Cancer Cells 2 -0.223 0.000 Erythrocytes/Cancer Cells 3 -0.221 0.000 PT N0---N12 4 0.199 0.000 Thrombocytes/Cancer Cells 5 -0.197 0.000 Leucocytes/Cancer Cells 6 -0.188 0.000 Prothrombin Index 7 0.163 0.000 Eosinophils/Cancer Cells 8 -0.161 0.000 Monocytes/Cancer Cells 9 -0.144 0.000 Tumor Size 10 0.143 0.000 Segmented Neutrophils/Cancer Cells 11 -0.134 0.000 PT Early---Invasive Cancer 12 -0.130 0.000 T1-4 13 0.126 0.000 Erythrocytes (tot) 14 -0.117 0.000 Segmented Neutrophils (%) 15 0.110 0.000 Lymphocytes (tot) 16 -0.108 0.000 Weight 17 -0.103 0.001 Lymphocytes (%) 18 -0.087 0.01 Eosinophils (tot) 19 -0.085 0.01 G1-3 20 0.083 0.01 Lymphocytes (abs) 21 -0.082 0.01 ESS 22 0.081 0.01 Heparin Tolerance 23 0.080 0.01 Stick Neutrophils/Cancer Cells 24 -0.077 0.01 Glucose 25 -0.071 0.01 Eosinophils (%) 26 -0.065 0.05 Only Surgery 27 -0.064 0.05 Eosinophils (abs) 28 -0.061 0.05 0 5 10 15 20 25 30 35 Lymphocytes/Cancer Cells 11.11.21.31.41.51.61.71.81.9 PT Early--Invasive Cancer 1 1 1.1 1.1 1.2 1.2 1.3 1.3 1.4 1.4 1.5 1.5 1.6 1.6 1.7 1.7 1.8 1.8 1.9 1.9 2 2 5-YearSurvival 5-YearSurvival P=0.0000 z=a+blnx+cy+d(lnx)^2+ey^2+fylnx+g(lnx)^3+hy^3+iy^2lnx+jy(lnx)^2 r^2=0.15389193 DF Adj r^2=0.13979013 FitStdErr=0.43174167 Fstat=12.145684 a=1.6730247 b=0.10714131 c=-1.559062 d=-0.054738649 e=2.0848282 f=-0.42449195 g=0.0015228759 h=-0.73551088 i=0.18814164 j=0.022282855 0 5 10 15 20 25 30 35 Lymphocytes/Cancer Cells 00.10.20.30.40.50.60.70.80.9 PT N0---N12 1 1 1.1 1.1 1.2 1.2 1.3 1.3 1.4 1.4 1.5 1.5 1.6 1.6 1.7 1.7 1.8 1.8 1.9 1.9 2 2 5-YearSurvival 5-YearSurvival P=0.0000 z=a+b/x+c/x^2+d/x^3+e/x^4+f/x^5+gy r^2=0.24088672 DF Adj r^2=0.23207446 FitStdErr=0.40792762 Fstat=31.944196 a=0.85682428 b=1.0401408 c=-1.0202475 d=0.47891711 e=-0.098874149 f=0.0071729116 g=0.37035265