Artificial Intelligence, System Analysis and Simulation Modeling
in Optimization of Management for Lung Cancer Patients
Oleg Kshivets, MD, PhD Surgery Department, Khimki Clinic N1, Moscow, Russia PS-01.40
OBJECTIVE: Search of best management for non-small lung cancer (LC) patients (LCP) (T1-4N0-2M0) was realized.
METHODS: We analyzed data of 672 consecutive LCP (age=57.5±8.3 years; tumor size=4.4±2.4 cm) radically operated and
monitored in 1985-2016 (m=581, f=91; lobectomies=430, pneumonectomies=242, combined procedures with resection of trachea,
carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=184; only surgery=530, adjuvant
chemoimmunoradiotherapy-AT=142: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=239, T2=249, T3=129,
T4=55; N0=425, N1=130, N2=117, M0=672; G1=168, G2=201, G3=303; squamous=380, adenocarcinoma=247, large cell=45; early
LC=134, invasive LC=538. 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 2104.2±1685.2 days and cumulative 5-year survival (5YS) reached 69.7%, 10 years – 61.9%,
20 years – 42.5%. 417 LCP lived more than 5 years (LS=3044.7±1472.2 days), 109 LCP – more than 10 years (LS=5048±1471.6 days).
194 LCP died because of LC (LS=560.7±372.9 days). AT significantly improved 5YS (65.3% vs. 34.3%) (P=0.00001 by log-rank test)
only for LCP with N1-2. Cox modeling displayed (Chi2=292.44, df=13, P=0.000) that 5YS of LCP significantly depended on: phase
transition (PT)“early-invasive LC” in terms of synergetics, 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=0.000-0.033). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between
5YS and PT“early-invasive LC” (rank=1), PT N0-N12 (rank=2), AT (3), segmented neutrophils (4), lymphocytes (5), prothrombin
index (6),healthy cells/CC (7), T1-4 (8), tumor size (9), thrombocytes/CC (10), erythrocytes/CC (11),lymphocytes/CC (12). Correct
prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
CONCLUSIONS: Optimal management for LCP are: 1) screening and early detection of LC; 2) availability of experienced thoracic
surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for
completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Parameter Estimates:Chi2=292.44, df=13, P=0.0000, n=672
Cox Regression Parameter
Estimate
Standard
Error
Chi-
square
P value 95%
Lower CL
95%
Upper CL
Hazard
Ratio
95%
HazardRatio
Lower CL
95%
HazardRatio
Upper CL
Histology 0.29021 0.087856 10.91150 0.000956 0.11802 0.462408 1.336711 1.125263 1.587893
G1-3 0.32570 0.089528 13.23471 0.000275 0.15023 0.501169 1.384997 1.162098 1.650649
Phase Transition Early-Invasive Cancer -1.32520 0.393120 11.36353 0.000749 -2.09570 -0.554700 0.265749 0.122984 0.574244
Adjuvant Chemoimmunoradiotherapy -1.01228 0.201036 25.35421 0.000000 -1.40630 -0.618253 0.363391 0.245048 0.538885
Phase Transition N0--N12 1.06470 0.147841 51.86362 0.000000 0.77493 1.354459 2.899959 2.170449 3.874666
Glucose -0.29033 0.081154 12.79817 0.000347 -0.44938 -0.131266 0.748020 0.638020 0.876984
Prothrombin Index 0.03002 0.006828 19.32862 0.000011 0.01664 0.043400 1.030473 1.016775 1.044356
Recalcification Time -0.00585 0.001771 10.92016 0.000951 -0.00932 -0.002381 0.994166 0.990722 0.997622
Heparin Tolerance 0.00366 0.000667 30.07778 0.000000 0.00235 0.004965 1.003665 1.002353 1.004977
Eosinophils/Cancer Cells -0.99120 0.425130 5.43595 0.019726 -1.82443 -0.157957 0.371133 0.161309 0.853887
Lymphocytes/Cancer Cells -0.17877 0.067403 7.03422 0.007997 -0.31088 -0.046660 0.836300 0.732805 0.954412
Erythrocytes (tot) -0.03803 0.017819 4.55381 0.032846 -0.07295 -0.003101 0.962688 0.929647 0.996904
Thrombocytes (tot) 0.00050 0.000191 6.81611 0.009034 0.00012 0.000872 1.000498 1.000124 1.000872
Neural Networks: n=611
Baseline Error=0.000;
Area under ROC Curve=1.000;
Correct Classification Rate=100%
Rank Sensitivity
PT Early---Invasive Cancer 1 9516
PT N0---N12 2 9479
Adjuvant Chemoimmunoradiotherapy 3 6705
Segmented Neutrophils 4 5951
Lymphocytes 5 5894
Prothrombin Index 6 5126
Healthy Cells/Cancer Cells 7 5034
T1-4 8 4255
Tumor Size 9 3525
Thrombocytes/Cancer Cells 10 2840
Erythrocytes/Cancer Cells 11 2740
Lymphocytes/Cancer Cells 12 2170
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 0.197 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
Seg.Neutrophils/Cancer Cells 11 -0.134 0.000
PT Early---Invasive Cancer 12 -0.131 0.000
T1-4 13 -0.124 0.000
Lymphocytes (tot) 14 -0.108 0.000
Erythrocytes (tot) 15 -0.117 0.000
Segmented Neutrophils (%) 16 0.109 0.000
Weight 17 -0.105 0.000
Eosinophils (tot) 18 -0.085 0.01
Lymphocytes (%) 19 -0.086 0.01
G1-3 20 0.083 0.01
ESS 21 0.082 0.01
Lymphocytes (abs) 22 -0.082 0.01
Heparin Tolerance 23 0.078 0.01
Stick Neutrophils/Cancer Cells 24 -0.077 0.01
Glucose 25 -0.072 0.01
Only Surgery 26 -0.065 0.05
Eosinophils (%) 27 -0.063 0.05
Eosinophils (abs) 28 -0.059 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