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ARTIFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION
       MODELING IN OPTIMIZATION OF LUNG CANCER TREATMENT
 Oleg Kshivets, Siauliai, Lithuania, 5th EACTS/ESTS JOINT MEETING, 9-13 September 2006, Stockholm, Sweden

METHODS: In trial (1985-2006) the data                                                                                                                                                                       It was revealed that 5YS and LS of LCP
of consecutive 425 LCP (age=56.4;                                                                                                                                                                            after resections significantly depended on:
m=382, f=43; D=4.4 cm; pn=185, lob=240,                                                                                                                                                                     1) phase transition "early LC-invasive LC";
comb=63; sq=274, ad=124, lcl=27;                                                                                                                                                                            2) level of blood cell subpopulations circuit;
T1=124, T2=196, T3=86, T4=19; N0=234,                                                                                                                                                                       3) ratio LC cells/blood cell subpopulations;
N1=104, N2=87) was reviewed. Neural
                                                                                                                                                                                                            4) LC characteristics;
networks computing, Cox regression,
clustering, discriminant analysis, structural                                                                                                                                                               5) hemostasis system;
equation modeling, Monte Carlo and                                                                                                                                                                          6) biochemic data;
bootstrap simulation were used to                                                                                                                                                                           7) hematological factors;
determine any significant regularity.                                                                                                                                                                       8) procedure type; anthropometric data.

RESULTS: Overall LS=1674.5±54.1 days                                                                                                                                                                        Correct prediction of LCP survival after
and 5YS reached 59.1%. 251 LCP lived                                                                                                                                                                        complete pneumonectomies and
more than 5 years (LS=2446.7±46.5 days).                                                                                                                                                                    lobectomies (R0) was 84% by logistic
174 LCP died because of LC during first 5                                                                                                                                                                   regression, 85.8% by discriminant analysis
years after surgery (LS=560.8±29.2 days).                                                                                                                                                                   and 100% by neural networks computing
          Cox Regression: Prediction of 5-Year Survival of Lung Cancer Patients after Complete Resections (n=425)

                                                                                                   95.0% CI for Exp(B)
                                                                                                                                                                                                            (error=0.0017; urea under ROC curve=1.0).
       AGE
       WEIGHT
                                   B
                                   .015
                                  -.007
                                            SE
                                            .007
                                            .005
                                                     Wald
                                                      4.155
                                                      1.821
                                                                df
                                                                     1
                                                                     1
                                                                          Sig.
                                                                            .042
                                                                            .177
                                                                                       Exp(B)
                                                                                         1.015
                                                                                          .993
                                                                                                   Lower
                                                                                                      1.001
                                                                                                       .984
                                                                                                                Upper
                                                                                                                  1.029
                                                                                                                  1.003
                                                                                                                                                                                   Cumulative Proportion Surviving (Kaplan-Meier)
                                                                                                                                                                                                     Complete     Censored
                                                                                                                                                                                  Survival of Lung Cancer Patients with N1-2 (n=191)
                                                                                                                                                                                                                                                             CONCLUSIONS: Optimal
       GROWTH                      .163     .111      2.164          1      .141         1.177         .947       1.463

                                                                                                                                                                                                                                                              treatment strategies for lung
                                                                                                                                                                                               P=0.0007 by Log Rank Test
       HISTOLOGY                   .053     .070       .572          1      .449         1.054         .920       1.208
       G1-3                        .067     .065      1.049          1      .306         1.069         .941       1.214                                      1.0
       T1-4                        .172     .089      3.769          1      .050         1.188         .998       1.413
                                                                                                                          Cumulative Proportion Surviving




                                                                                                                                                             0.9
                                                                                                                                                                                                           Without Adjuvant CHIRT, n=152
       N0-2
       TUMOR SIZE
       ERYTHROCYTES
                                   .343
                                   .023
                                  -.182
                                            .070
                                            .037
                                            .111
                                                     24.102
                                                       .388
                                                      2.662
                                                                     1
                                                                     1
                                                                     1
                                                                            .000
                                                                            .533
                                                                            .103
                                                                                         1.410
                                                                                         1.023
                                                                                          .834
                                                                                                      1.229
                                                                                                       .952
                                                                                                       .670
                                                                                                                  1.617
                                                                                                                  1.100
                                                                                                                  1.037
                                                                                                                                                             0.8
                                                                                                                                                             0.7
                                                                                                                                                             0.6
                                                                                                                                                                                                           Adjuvant CHIRT, n=39
                                                                                                                                                                                                                                                              cancer patients are:
       THROMBOCYTES                .002     .001      2.442          1      .118         1.002         .999       1.005
                                                                                                                                                             0.5
       LEUCOCYTES

                                                                                                                                                                                                                                                             1) screening and early detection of
                                  -.048     .024      3.893          1      .048          .953         .909       1.000
       STICK NEUTROPHILS          -.065     .027      6.072          1      .014          .937         .889        .987                                      0.4
       LYMPHOCYTES                -.021     .006     12.401          1      .000          .979         .968        .991                                      0.3
       ESS                        -.008     .005      3.059          1      .080          .992         .983       1.001                                      0.2
       GLUCOSE
       PROTHROMBIN INDEX
       BILIRUBIN
                                  -.085
                                   .026
                                   .037
                                            .058
                                            .006
                                            .018
                                                      2.117
                                                     16.778
                                                      4.118
                                                                     1
                                                                     1
                                                                     1
                                                                            .146
                                                                            .000
                                                                            .042
                                                                                          .918
                                                                                         1.026
                                                                                         1.037
                                                                                                       .819
                                                                                                      1.014
                                                                                                      1.001
                                                                                                                  1.030
                                                                                                                  1.039
                                                                                                                  1.075
                                                                                                                                                             0.1
                                                                                                                                                                      0       2         4        6         8       10
                                                                                                                                                                                     Years after Pneomonectomies & Lobectomies
                                                                                                                                                                                                                              12        14   16   18          lung cancer;
       PROTEIN                    -.010     .008      1.676          1      .195          .990         .976       1.005
       RECALCIFICATION TIME
       FIBRINOGEN
       HEPARIN TOLERANCE
                                  -.004
                                   .057
                                   .003
                                            .001
                                            .038
                                            .001
                                                      6.672
                                                      2.329
                                                     31.258
                                                                     1
                                                                     1
                                                                     1
                                                                            .010
                                                                            .127
                                                                            .000
                                                                                          .996
                                                                                         1.059
                                                                                         1.003
                                                                                                       .993
                                                                                                       .984
                                                                                                      1.002
                                                                                                                   .999
                                                                                                                  1.140
                                                                                                                  1.005
                                                                                                                                                                                                Training Error Graph (Sum-squared)
                                                                                                                                                                                            Prediction of 5-Year Survival of LCP (n=425)
                                                                                                                                                                                                                                                             2) aggressive en block surgery for
      Cox Regression: Prediction of 5-Year Survival of Lung Cancer Patients after Complete Resections (n=425)

                                                                                                   95.0% CI for Exp(B)
                                                                                                                                                                                                          Network: 10 (MLP)
                                                                                                                                                                                   Baseline Error=0.0017; Correct Classification Rate=100%
                                                                                                                                                                                                  Area Under ROC Curve=1.00
                                                                                                                                                                                                                                                              completeness;
                                            B          SE        Wald      df   Sig.     Exp(B)     Lower      Upper                                                0.6
      THROMBOCYTES/CANCER CELL
      LEUCOCYTES/CANCER CELLS
      STICK NEUTROPHILS/CANCER C
                                            -.010
                                            -.790
                                            1.552
                                                        .003
                                                        .479
                                                       1.156
                                                                 10.265
                                                                  2.717
                                                                  1.803
                                                                           1
                                                                           1
                                                                           1
                                                                                .001
                                                                                .099
                                                                                .179
                                                                                            .991
                                                                                            .454
                                                                                           4.721
                                                                                                       .985
                                                                                                       .178
                                                                                                       .490
                                                                                                                  .996
                                                                                                                 1.161
                                                                                                                45.499                                              0.4
                                                                                                                                                                                  Train by Levenberg-Marquardt
                                                                                                                                                                                                                                                             3) precise prediction;
      SEGM.NEUTROPHILS/CANCER C              .861       .515      2.794    1    .095       2.365       .862      6.490

                                                                                                                                                                                                                                                             4) adjuvant CHIRT for lung cancer
                                                                                                                                                            Error




      LYMPHOCYTES/CANCER CELLS               .885       .577      2.353    1    .125       2.424       .782      7.513
      NORM CELLS/CANCER CELLS                .117       .039      8.901    1    .003       1.125      1.041      1.215
                                                                                                                                                                    0.2
      THROMBOCYTES (tot)                     .003       .001     13.951    1    .000       1.003      1.001      1.004
      LEUCOCYTES (tot)
      STIC NEUTROPHILS (tot)
      SEGMENTED NEUTROPHILS (tot
                                             .192
                                            -.603
                                            -.327
                                                        .130
                                                        .302
                                                        .148
                                                                  2.172
                                                                  3.980
                                                                  4.866
                                                                           1
                                                                           1
                                                                           1
                                                                                .141
                                                                                .046
                                                                                .027
                                                                                           1.212
                                                                                            .547
                                                                                            .721
                                                                                                       .939
                                                                                                       .303
                                                                                                       .539
                                                                                                                 1.564
                                                                                                                  .989
                                                                                                                  .964
                                                                                                                                                                    0.0
                                                                                                                                                                          0        10                20           30               40        50        60
                                                                                                                                                                                                                                                              patients with unfavorable
                                                                                                                                                                                                                                                              prognosis.
      LYMPHOCYTES (tot)                     -.298       .158      3.565    1    .059        .742       .545      1.011                                                                                          Epoch
      SEGMENTED NEUTROPHILS (abs             .608       .171     12.634    1    .000       1.836      1.313      2.566



                                                                                                                                                                                                                                                                              Poster Nr.

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  • 1. ARTIFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN OPTIMIZATION OF LUNG CANCER TREATMENT Oleg Kshivets, Siauliai, Lithuania, 5th EACTS/ESTS JOINT MEETING, 9-13 September 2006, Stockholm, Sweden METHODS: In trial (1985-2006) the data It was revealed that 5YS and LS of LCP of consecutive 425 LCP (age=56.4; after resections significantly depended on: m=382, f=43; D=4.4 cm; pn=185, lob=240, 1) phase transition "early LC-invasive LC"; comb=63; sq=274, ad=124, lcl=27; 2) level of blood cell subpopulations circuit; T1=124, T2=196, T3=86, T4=19; N0=234, 3) ratio LC cells/blood cell subpopulations; N1=104, N2=87) was reviewed. Neural 4) LC characteristics; networks computing, Cox regression, clustering, discriminant analysis, structural 5) hemostasis system; equation modeling, Monte Carlo and 6) biochemic data; bootstrap simulation were used to 7) hematological factors; determine any significant regularity. 8) procedure type; anthropometric data. RESULTS: Overall LS=1674.5±54.1 days Correct prediction of LCP survival after and 5YS reached 59.1%. 251 LCP lived complete pneumonectomies and more than 5 years (LS=2446.7±46.5 days). lobectomies (R0) was 84% by logistic 174 LCP died because of LC during first 5 regression, 85.8% by discriminant analysis years after surgery (LS=560.8±29.2 days). and 100% by neural networks computing Cox Regression: Prediction of 5-Year Survival of Lung Cancer Patients after Complete Resections (n=425) 95.0% CI for Exp(B) (error=0.0017; urea under ROC curve=1.0). AGE WEIGHT B .015 -.007 SE .007 .005 Wald 4.155 1.821 df 1 1 Sig. .042 .177 Exp(B) 1.015 .993 Lower 1.001 .984 Upper 1.029 1.003 Cumulative Proportion Surviving (Kaplan-Meier) Complete Censored Survival of Lung Cancer Patients with N1-2 (n=191) CONCLUSIONS: Optimal GROWTH .163 .111 2.164 1 .141 1.177 .947 1.463 treatment strategies for lung P=0.0007 by Log Rank Test HISTOLOGY .053 .070 .572 1 .449 1.054 .920 1.208 G1-3 .067 .065 1.049 1 .306 1.069 .941 1.214 1.0 T1-4 .172 .089 3.769 1 .050 1.188 .998 1.413 Cumulative Proportion Surviving 0.9 Without Adjuvant CHIRT, n=152 N0-2 TUMOR SIZE ERYTHROCYTES .343 .023 -.182 .070 .037 .111 24.102 .388 2.662 1 1 1 .000 .533 .103 1.410 1.023 .834 1.229 .952 .670 1.617 1.100 1.037 0.8 0.7 0.6 Adjuvant CHIRT, n=39 cancer patients are: THROMBOCYTES .002 .001 2.442 1 .118 1.002 .999 1.005 0.5 LEUCOCYTES 1) screening and early detection of -.048 .024 3.893 1 .048 .953 .909 1.000 STICK NEUTROPHILS -.065 .027 6.072 1 .014 .937 .889 .987 0.4 LYMPHOCYTES -.021 .006 12.401 1 .000 .979 .968 .991 0.3 ESS -.008 .005 3.059 1 .080 .992 .983 1.001 0.2 GLUCOSE PROTHROMBIN INDEX BILIRUBIN -.085 .026 .037 .058 .006 .018 2.117 16.778 4.118 1 1 1 .146 .000 .042 .918 1.026 1.037 .819 1.014 1.001 1.030 1.039 1.075 0.1 0 2 4 6 8 10 Years after Pneomonectomies & Lobectomies 12 14 16 18 lung cancer; PROTEIN -.010 .008 1.676 1 .195 .990 .976 1.005 RECALCIFICATION TIME FIBRINOGEN HEPARIN TOLERANCE -.004 .057 .003 .001 .038 .001 6.672 2.329 31.258 1 1 1 .010 .127 .000 .996 1.059 1.003 .993 .984 1.002 .999 1.140 1.005 Training Error Graph (Sum-squared) Prediction of 5-Year Survival of LCP (n=425) 2) aggressive en block surgery for Cox Regression: Prediction of 5-Year Survival of Lung Cancer Patients after Complete Resections (n=425) 95.0% CI for Exp(B) Network: 10 (MLP) Baseline Error=0.0017; Correct Classification Rate=100% Area Under ROC Curve=1.00 completeness; B SE Wald df Sig. Exp(B) Lower Upper 0.6 THROMBOCYTES/CANCER CELL LEUCOCYTES/CANCER CELLS STICK NEUTROPHILS/CANCER C -.010 -.790 1.552 .003 .479 1.156 10.265 2.717 1.803 1 1 1 .001 .099 .179 .991 .454 4.721 .985 .178 .490 .996 1.161 45.499 0.4 Train by Levenberg-Marquardt 3) precise prediction; SEGM.NEUTROPHILS/CANCER C .861 .515 2.794 1 .095 2.365 .862 6.490 4) adjuvant CHIRT for lung cancer Error LYMPHOCYTES/CANCER CELLS .885 .577 2.353 1 .125 2.424 .782 7.513 NORM CELLS/CANCER CELLS .117 .039 8.901 1 .003 1.125 1.041 1.215 0.2 THROMBOCYTES (tot) .003 .001 13.951 1 .000 1.003 1.001 1.004 LEUCOCYTES (tot) STIC NEUTROPHILS (tot) SEGMENTED NEUTROPHILS (tot .192 -.603 -.327 .130 .302 .148 2.172 3.980 4.866 1 1 1 .141 .046 .027 1.212 .547 .721 .939 .303 .539 1.564 .989 .964 0.0 0 10 20 30 40 50 60 patients with unfavorable prognosis. LYMPHOCYTES (tot) -.298 .158 3.565 1 .059 .742 .545 1.011 Epoch SEGMENTED NEUTROPHILS (abs .608 .171 12.634 1 .000 1.836 1.313 2.566 Poster Nr.