Transcript
Immunity Netwoks in Prediction of Five-Year Survival of Lung Cancer Patients after Radical Procedures
Oleg Kshivets, M.D., Ph.D.Department of Surgery, Siauliai Cancer Center, Lithuania
The First International Chicago Symposium on Malignancies of The Chest and Head & Neck
Chicago, Illinois, The USA, 1999
Abstracts: Purpose: Influence of immunity networks on 5-year survival (5YS) of lung cancer (LC) patients (LCP) after a
radical procedure (RP) was investigated. Methods: In randomized trial (1987-1998) cases after RP, monitored 108 LCP (males – 94, females – 14;
pneumonectomy - 45, upper lobectomy - 44, lower lobectomy - 11, upper/lower bilobectomy - 5, middle lobectomy -1) with pathologic stage II-III (stage II – 34, stage III – 74; squamos cell LC - 56, adenocarcinoma - 46, large cell LC - 6; T1 - 38, T2 - 43, T3 – 23, T4 - 4; N0 – 63, N1 - 20, N2 - 25; G1 – 30, G2 – 34, G3 - 44) were reviewed. 59 LCP (age=56.70.9 years; tumor size: D=4.30.3 cm; life span: LS=1903.821.0 days) lived more than 5 years without any features of LC progressing. 49 LCP (age=56.61.2 years; D=4.60.3 cm; LS=542.755.2 days) died because of generalization of LC during the first 5 years after RP. Variables selected for 5YS study were input levels of 49 immunity blood parameters, sex, age, TNMG, cell type, D. Representativeness of samplings was reached by means of randomization based on unrepeated random selection. Multiple correspondence analysis (A), multi-factor clustering, A of variance, confirmatory factor A, structural equation modeling and Monte Carlo simulation were used to determine any significant overall regularity.
Results: It was revealed that 5YS of LCP (n=108) after RP significantly depended on: 1) level of T-, B- and O-cell circuit; 2) value of monocyte- and macrophage-circuit; 3) level of humoral immunity; 4) ratio of malignant cell population quantity to immunity cell subpopulations in integral patient’s organism (cell ratio factors); 5) LC characteris-tics. Structural equation modeling and Monte Carlo simulation confirmed signifi-cant overall networks bet-ween 5YS (life span) of LCP after RP and cell immunity circuit (2=7744.820;k=628; T=2.264;P=0.024), humoral immunity data (2=20.328; k=13; T=3.496; P=0.0005), cell ratio factors (2=446.462; k=65; T=13.258; P=0.0001e-9), LC characteristics (2=69.514; k=19; T=4.520; P=0.00062e-2).
Samplings:
Lung Cancer Patients Lived More than 5 Years after Radical Procedures……….59
Lung Cancer Patients Died Because Generalization During First 5 Years After Radical Procedures……………...49
In All……………………………… …108
Radical Procedures:
Pneumonectomy…………………..45 Upper/Lower Bilobectomy……...…7 Upper Lobectomy………………....44 Lower Lobectomy………………....11 Middle Lobectomy………………….1 In All…………………………...…108
Staging:
T1……38 N0……63 G1……30 T2……43 N1……20 G2……34 T3……23 N2……25 G3……44 T4……..4 Stage II…34 Stage III...74 Squamous Cell Carcinoma……….....…56 Adenocarcinoma……………………….46 Large Cell Carcinoma…………………..6
Regularities between Lung Cancer Cell Population and Suvival:
Bivariate Histogram: D and SURVIVALRelationships between Life Span and Cancer Diameter
Immunology of Lung Cancer Patients (n=108)
Regularities between Immune System and 5-Year Survival Lung Cancer Patients:
Immune Homeostasis in Prognosis Lung Cancer Patients Survival:
Nucloids of Immune Cell Ratio Factors in Prognosis 5-Year Survival Lung Cancer Patients:
Correlations of Immune Cell Ratio Factors with Lung Cancer Patients Survival:
From: Correlations (ilc1.sta)Marked correlations are significant at p < ,05000
Immunology of Lung Cancer Patients (n=108 )Relationships between Cell Ratio Factors and Survival
SEPATH-Model: Immune Cell Ratio Factors-Survival Lung Cancer Patients:
Normal Probability PlotNormalized Residuals
Immunology of Lung Cancer (n=108) Model: Immune Cell Ratio Factors--Survival
chi-square=275.261; df=43; P<0.0000001;
Value
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d N
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-2,5 -1,5 -0,5 0,5 1,5 2,5 3,5
Immune Cell Ratio Factors in Prediction 5-Year Survival:
Logistic Regression Model: Immune Cell Ratio
Factors-Survival Lung Cancer Patients: Normal Probability Plot of Residuals
Immunology of Lung Cancer Patients (n=108)Logistic Regression
Immune Cell Ratio Factors--5Year SurvivalChi-square=36.996; df=9; P=0.000027;
Residuals
Expe
cted
Nor
mal
Val
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-3
-2
-1
0
1
2
3
-1,2 -0,8 -0,4 0,0 0,4 0,8 1,2
Logistic Regression Model of System:Immune Cell Ratio Factors-Survival Lung Cancer
Patients:Correlations (ILC1.STA 117v*108c)
Immune Cell Ratio Factors -5-Year SurvivalImmunology of Lung Cancer Patients (n=108)
Logistic Regression
T_CC
B_CC
O_CC
TR_CC
TB_CC
TV_CC
TS_CC
TFC_CC
TFR_CC
SURV5Y
Models (T/CC, CD8+/CC and CD4+/CC, Lymph/CC-Life Span of LCP; n=49; 18th:P<0.01; 12th:P<0.001; 6th: P<0.05 and 18th: P<0.01 Degree Polynomial Fit):
y=a+bx+cx2+dx 3+… S = 374.72565504
r = 0.40486902
X Axis (units)
Y A
xis (
units
)
0.0 0.6 1.3 1.9 2.5 3.1 3.8
S = 372.39349244r = 0.63251294
X Axis (units)
Y A
xis (
units
)
0.0 0.1 0.3 0.4 0.6 0.7 0.8
S = 387.26431750r = 0.34782666
X Axis (units)
Y A
xis (
units
)
0.0 0.6 1.1 1.7 2.3 2.8 3.4
Lymph/CC-Life Span; S=433,101; r=0.4634; P<0.01
X Axis (units)
Y A
xis (
units
)
0.0 1.2 2.4 3.6 4.8 6.0 7.2
Regression Models (B/CC, O/CC and Mon/CC-Life Span of LCP; n=49; 18th: P<0.001;13th: P<0.01 and 18th: P<0.01 Degree Polynomial Fit): y=a+bx+cx2+dx 3+...
S = 385.67804334r = 0.61421827
X Axis (units)
Y A
xis (
units
)
0.0 0.3 0.5 0.8 1.0 1.3 1.6
S = 386.29195183r = 0.52073027
X Axis (units)
Y A
xis (
units
)
0.0 0.5 1.0 1.5 2.0 2.5 3.0
Mon/CC-Life Span, S=444.483; r=0.4158; P<0.01
X Axis (units)
Y A
xis (
units
)
0.0 0.2 0.4 0.7 0.9 1.1 1.3
IgG-Life Span, S=346,759; r=0.7047; P<0.001
X Axis (units)
Y A
xis (
units
)
1.1 5.8 10.5 15.2 19.9 24.6 29.4
IgA-Life Span, S=438.044; r=0.4435; P<0.01
X Axis (units)
Y A
xis (
units
)
0.7 2.1 3.4 4.7 6.0 7.3 8.7
IgM-Life Span, S=460.348; r=0.3358; P<0.05
X Axis (units)
Y A
xis (
units
)
0.5 1.2 1.9 2.6 3.3 4.0 4.6
Regression Models (IgG, IgA and IgM-Life Span of LCP; n=49; 18th Degree Polynomial Fit): y=a+bx+cx2+dx 3+...
SEPATH-Models: Immune Cell Circuit-Lung Cancer Patients Survival:
Normal Probability PlotNormalized Residuals
Immunology of Lung Cancer patients (n=108) Model: T-,B-,O-cell circuit--Survival
chi-square=6244.2; df=463; P<0.0000001;
Value
Exp
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d N
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al V
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-3
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Normal Probability PlotNormalized Residuals
Immunology of Lung Cancer Patients (n=108) Model: Macrophage circuit--Survivalchi-square=87.670; df=43; P=0.000068
Value
Exp
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d N
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al V
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-3
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-1
0
1
2
3
-3 -2 -1 0 1 2 3 4 5 6
Relationships between Immune Cell Subpopulations and Life Span of Lung Cancer Patients:
-0,319 -0,257 -0,195 -0,133 -0,071 -0,009 0,053 0,114 0,176 0,238 above
From: Correlations (ilc1.sta)Marked correlations are significant at p < ,05000
Immunology of Lung Cancer Patients (n=108)Relationships between Survival and Immune Cell Subpopulations
Immunity Networks and 5-Year Survival of Lung Cancer Patients
SEPATH-Models: Immune Homeostasis--Life Span of Lung Cancer Patients:
Normal Probability PlotNormalized Residuals
Immunology of Lung Cancer Patients (n=108) Model: T-,B-,O-cell circuit--Humor.Immunity--Cell Ratio Factors--Biochem.Homeost
Value
Exp
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d N
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al V
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-3
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0
1
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-8 -4 0 4 8 12
Normal Probability PlotNormalized Residuals
Immunology of Lung Cancer (n=108) Model:T,B,O-circuit-Cancer-Humor.Immun.-Makroph.Circ.-Blood-Biochemy
Value
Exp
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d N
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al V
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-12 -8 -4 0 4 8 12
SEPATH-Models: Humoral Immunity, Cancer Cell Population-Life Span of Lung
Cancer Patients:Normal Probability PlotNormalized Residuals
Immunology of Lung Cancer Patients (n=108)Model: Humoral immunity--Survival
chi-square=23.534; df=13; P=0.036;
Value
Exp
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d N
orm
al V
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-2,5
-1,5
-0,5
0,5
1,5
2,5
-4 -2 0 2 4 6 8
Normal Probability PlotNormalized Residuals
Immunology of Lung Cancer Patients (n=108) Model: Cancer Cell Population--Survivalchi-square=183.673; df=34; P<0.0000001;
Value
Exp
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d N
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al V
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-4 -2 0 2 4 6 8
Results of Monte Carlo Simulation:
-1,684 -1,289 -0,895 -0,500 -0,105 0,289 0,684 1,079 1,474 1,868 above
From: Monte Carlo Data (ilc1.sta)
Immunology of Lung Cancer Patients (n=108)Monte Carlo Simulation: T-, B-, O-circuit--Survival
-1,702 -1,370 -1,037 -0,704 -0,372 -0,039 0,294 0,627 0,959 1,292 above
From: Monte Carlo Data (ilc1.sta)Immunology of Lung Cancer Patients (n=108)
Monte Carlo Simulation: Humoral Homeostasis--Survival
-1,211 -0,804 -0,396 0,011 0,419 0,826 1,234 1,641 2,049 2,456 above
From: Monte Carlo Data (ilc1.sta)Immunology of Lung Cancer Patients (n=108)
Monte Carlo Simulation: Macrophage Circuit--Survival
-2,252 -2,004 -1,756 -1,508 -1,260 -1,012 -0,764 -0,516 -0,268 -0,020 above
From: Monte Carlo Data (ilc1.sta)Immunology of Lung Cancer Patients (n=108)
Monte Carlo Simulation: Immune Cell Ratio Factors--Survival
Results of Monte Carlo Simulation: Cancer Cell Population--Survival:
-0,976 -0,736 -0,495 -0,254 -0,014 0,227 0,467 0,708 0,949 1,189 above
From: Monte Carlo Data (ilc1.sta)Immunology of Lung Cancer Patients (n=108)
Monte carlo Simulation: Cancer Cell Population--Survival
Networks between Immune Cell Subpopulations, Cancer Cell Populations and 5-Year Survival
Lung Cancer Patients:
Conclusions:
5-year survival and lifevspan of lung cancer patients after radical procedures significantly depended on:
1) level of T-, B- and O-cell circuit; 2) value of monocyte- and macrophage-circuit; 3) level of humoral immunity; 4) ratio of malignant cell population quantity to
immunity cell subpopulations in integral patient’s organism (immune cell ratio factors);
5) cancer characteristics.
Oleg Kshivets, M.D., Ph.D. Thoracic/Abdominal Surgeon, Department of Surgery
Siauliai Cancer Center, Tilzes:42-16, Siauliai, LT78206, Lithuania Tel. (37041)416614; Fax (37041)526430
okshivets@yahoo.com kshivets@hotmail.com http//:myprofile.cos.com/Kshivets
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