kshivets o. lung cancer surgery

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

Exp

ecte

d N

orm

al V

alue

-3

-2

-1

0

1

2

3

-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

ue

-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

ecte

d N

orm

al V

alue

-4

-3

-2

-1

0

1

2

3

4

-8 -4 0 4 8 12

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

ecte

d N

orm

al V

alue

-3

-2

-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

ecte

d N

orm

al V

alue

-4

-3

-2

-1

0

1

2

3

4

-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

ecte

d N

orm

al V

alue

-4

-3

-2

-1

0

1

2

3

4

-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

ecte

d N

orm

al V

alue

-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

ecte

d N

orm

al V

alue

-3

-2

-1

0

1

2

3

-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