Artificial Intelligence, System Analysis and Simulation Modeling in Optimization of Management for Lung Cancer Patients

1. 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