kshivets o. lung cancer stage iii surgery

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PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS WITH STAGE III CELL LUNG CANCER PATIENTS WITH STAGE III AFTER COMPLETE RESECTIONS AFTER COMPLETE RESECTIONS Oleg Kshivets, MD, PhD Oleg Kshivets, MD, PhD Department of Surgery, Siauliai Cancer Center, Department of Surgery, Siauliai Cancer Center, Siauliai, Lithuania Siauliai, Lithuania 2004 ASCO Annual Meeting, 2004 ASCO Annual Meeting, New Orleans, Louisiana, the USA, June 3-8, 2004 New Orleans, Louisiana, the USA, June 3-8, 2004

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Page 1: Kshivets O. Lung Cancer Stage III Surgery

PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS WITH STAGE III CELL LUNG CANCER PATIENTS WITH STAGE III

AFTER COMPLETE RESECTIONSAFTER COMPLETE RESECTIONS

Oleg Kshivets, MD, PhD Oleg Kshivets, MD, PhD Department of Surgery, Siauliai Cancer Center, Siauliai, LithuaniaDepartment of Surgery, Siauliai Cancer Center, Siauliai, Lithuania

2004 ASCO Annual Meeting,2004 ASCO Annual Meeting, New Orleans, Louisiana, the USA, June 3-8, 2004New Orleans, Louisiana, the USA, June 3-8, 2004

Page 2: Kshivets O. Lung Cancer Stage III Surgery

AbstractAbstract PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER

PATIENTS WITH STAGE III AFTER COMPLETE RESECTIONS Oleg Kshivets Surgery Department, Siauliai Cancer Center, Lithuania

OBJECTIVE: The influence of clinicomorphological data on 5-year survival (5YS) and life span (LS) of non-small lung cancer (LC) patients (LCP) with stage IIIA and IIIB after radical resections (R0) was investigated. METHODS: In trial (1985-2003) the data of consecutive 139 LCP (age=57.8±0.6 years; male=129, female=10; tumor diameter: D=5.6±0.2 cm; pneumonectomy=75, upper lobectomy=40, lower lobectomy=17, middle lobectomy=1, bilobectomy=6, combined procedures with resection of pericardium, left atrium, aorta, v. cava superior, carina, diaphragm, ribs=67; only surgery=54, adjuvant chemoimmunoradiotherapy-AT=40: CAV/gemzar-cisplatin + thymalin/taktivin + radiotherapy=40, postoperative radiotherapy-PR=45) with stage III (squamous cell=94, adenocarcinoma=34, large cell=11; stage IIIA=109, stage IIIB=30; T1=11, T2=48, T3=50, T4=30; N0=13, N1=32, N2=94; G1=24, G2=31, G3=84) was reviewed. Variables selected for 5YS study were input levels of blood, biochemic and hemostatic factors, sex, age, TNMG, D. Survival curves were estimated by Kaplan-Meier method. Differences in curves between groups were evaluated using a log-rank test. Neural networks computing, Cox regression, clustering, discriminant analysis, structural equation modeling and Monte Carlo simulation were used to determine any significant regularity. RESULTS: General life span was 1019.382.9 days (median=519). 49 LCP (35.3%) were alive, 44 from them lived more than 5 years (31.7%) without any features of progressing. 87 LCP (62.6%) died because of relapses and generalization during the first 5 years after surgery. Cox modeling displayed that 5-year survival of LCP (n=139) after complete resections significantly depended on: N0-2 (P=0.027), histology (P=0.002), G1-3 (P=0.036), character of operation (P=0.010), AT (P=0.0003), 20 blood factors (P=0.001-0.044). Neural networks computing and genetic algorithm selection revealed relationships between 5-year survival of LCP and AT (rank=1), G1-3 (2), PR (3), N0-2 (4), tumor growth (5), histology (6), procedure type (7), stage IIIA/IIIB (8), percent of monocytes (9), ESS (10). Correct prediction of LCP survival after radical procedures was 75.6% by logistic regression (odds ratio=7.57), 85.5% by discriminant analysis and 100% by neural networks computing (area under ROC curve=1.0; error=0.0027).

Page 3: Kshivets O. Lung Cancer Stage III Surgery

Factors:1) Antropometric Factors…………...42) Blood Analysis…………………...263) Hemostasis Factors……………….84) Cell Ratio Factors………………...9 5) Lung Cancer Characteristics…….86) Biochemic Factors………………...57) Treatment Characteristics……….58) Survival Data……………………...3 In All……………………………….68

Page 4: Kshivets O. Lung Cancer Stage III Surgery

Main Problem of Analysis of Alive Supersystems Main Problem of Analysis of Alive Supersystems (e.g. Lung Cancer Patient Homeostasis):(e.g. Lung Cancer Patient Homeostasis):

Phenomenon of «Combinatorial Explosion» Phenomenon of «Combinatorial Explosion»

Number of Factors:……………………………...….. 68Number of Possible Combination for Random Search:……………..………………….. n!=68!=2.5e+96 Operation Time of The 7G Superteracomputer (1000TFLOPS) (The 21st Century)…….7.9e+73 Years

Age of Universe………………………….1.3e+13 Years

Page 5: Kshivets O. Lung Cancer Stage III Surgery

Basis:Basis:

NP RP P n! n*n*2(e+n) or n log n n AI CSA+S+B SM

Page 6: Kshivets O. Lung Cancer Stage III Surgery

Radical Procedures:Radical Procedures:Pneumonectomy………………..75Upper/Lower Bilobectomy…...…6Upper Lobectomy…………...…40Lower Lobectomy……………...17Middle Lobectomy………….…...1In All…………………………...139

Page 7: Kshivets O. Lung Cancer Stage III Surgery

Combined & Extensive Radical Procedures with Resection of Pericardium, Left Atrium, Aorta, Vena Cava Superior, Vena Azygos, Carina, Trachea, Diaphragm, Chest Wall, Ribs, etc…..…………………….67

Sistematic MediastinalSistematic MediastinalLymph Node-N2 Lymph Node-N2 Dissection…………..Dissection…………..139139

Page 8: Kshivets O. Lung Cancer Stage III Surgery

Staging:Staging:T1…….11 N0..…..13 G1…..24T2…….48 N1……32 G2…..31T3…….50 N2……94 G3…..84T4…….30 Stage IIIA...109 Stage IIIB...30Squamous Cell Carcinoma…..………….94Adenocarcinoma…………………………34Large Cell Carcinoma…………………...11

Page 9: Kshivets O. Lung Cancer Stage III Surgery

Samplings:Samplings:

Adjuvant Chemoimmunoradiotherapy ……..40P/O Radiotherapy …...………………………..45Surgery Alone ……..…………………………..54In All…………………………………………..139

Male……………………………………….…..129 Female……...…………………………………..10Age=57.8±0.6 years

Page 10: Kshivets O. Lung Cancer Stage III Surgery

Adjuvant Therapy after Complete ResectionsAdjuvant Therapy after Complete ResectionsAdjuvant Chemoimmunoradiotherapy: 1 cycle of bolus chemotherapy (CAVT) was initiated 10-14 days after resections and consisted of Cyclophosphamid 500 mg/m2 IV on day 1, Doxorubicin 50 mg/m2 IV on day 1, Vincristin 1.4 mg/m2 IV on day 1. Immunotherapy consisted Thymalin or Taktivin 20 mg IM on days 1, 2, 3, 4 and 5. Chest radiotherapy (45-50 Gy) was administered since 7 day after 1 cycle chemoimmunotherapy at a daily dose of 1.8-2 Gy. No prophylactic cranial irradiation was used. From 2 to 3 weeks after completion of radiotherapy 3-4 courses of CAVT were repeated every 21-28 day. Chemotherapy by gemzar 1250 mg/m2 IV on day 1, 8, 15 and cisplatin 75 mg/m2 on day 1 was initiated on 14 day after surgery and was repeated every 14 day (5-6 courses). P/o Radiotherapy: Radiotherapy (60CO; ROKUS, Russia) with a total tumor dose 45-50 Gy (2-4 weeks after surgery) consisted of single daily fractions of 180-200 cGy 5 days weekly. The treatment volume included the ipsilateral hilus, the supraclavicular fossa and the mediastinum from the incisura jugularis to 5-7 cm below the carina. The lower mediastinum was included in cases of primary tumors in the lower lobes. The resected tumor bed was included in all patients. Parallel-opposed AP-PA fields were used. All fields were checked using the treatment planning program COSPO. Doses were specified at middepth for parallel-opposed technique or at the intersection of central axes for oblique technique. No prophylactic cranial irradiation was used.

Page 11: Kshivets O. Lung Cancer Stage III Surgery

Survival Rate of Lung Cancer Patients with Survival Rate of Lung Cancer Patients with Stage III after Complete Resections (n=139):Stage III after Complete Resections (n=139):

Alive………………………………………….49 (35.3%)5-Year Survivors…………………………….44 (31.7%) Losses from Lung Cancer…………………..87 (62.6%)Life Span=1019.3±82.9 days 5-Year Survivors with Stage IIIA………….38 (34.9%)5-Year Survivors with Stage IIIB…………...6 (20%)5-Year Survivors after Surgery alone……...11(20.4%)5-Year Survivors after P/o Radiotherapy.…14(31.1%)5-Year Survivors after Adjuvant Chemoimmunoradiotherapy………………..18 (45%)At All………….………………………………139 (100%)

Page 12: Kshivets O. Lung Cancer Stage III Surgery

Significant Factors between Lung Cancer Losses & 5-Year Survivors with Stage III (n=131)

Factors Mean±SD Mean±SD (Survivors) (Losses) P n=44 n=87Weight (kg) 72.3±12.3 66.8±12.2 0.016Seg.Neutrophiles (%) 64.9±11.9 69.2±9.7 0.030Monocytes (%) 5.5±2.8 4.3±2.8 0.021Prothrombin Index (%) 94.8±6.9 99.0±8.2 0.004Sul. Probe 1.95±0.17 1.86±0.19 0.009Fibrinogen-B 1.16±0.37 1.44±0.87 0.046

Life Span (days) 2283.5±684.6 424.9±309.1 0.0000

Log-Rank Test PN1 vs. N2 0.006Ad.CHIRT 0.0005Surgery Alone 0.015

Page 13: Kshivets O. Lung Cancer Stage III Surgery

Product-Limit (Kaplan-Maier) Analysis Results in Prediction of Lung Cancer Patients Survival with Stage III

after Complete Resections (n=139) Graph of Survival Times vs. Cum. Proportion Surviving

Survival FunctionComplete Censored

Prediction of Lung Cancer Patients Survival with Stage IIIn=139

Survival Years after Complete Resections

Cum

ulat

ive

Prop

ortio

n Su

rviv

ing

0.2

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0.4

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0.7

0.8

0.9

1.0

1.1

1.2

0 2 4 6 8 10 12 14 16 18

5-Year Survival

Page 14: Kshivets O. Lung Cancer Stage III Surgery

Cumulative Proportion Lung Cancer Patients Surviving (Kaplan-Meier) (n=139)

Cumulative Proportion Surviving (Kaplan-Meier)Complete Censored

Prediction of Lung Cancer Patients Survival with Stage IIIChi2=7.404; df=2; P=0.025; n=139

Years after Complete Resections

Cum

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ive

Prop

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0.1

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Lung Cancer Patients, Stage III with N0; n=13Lung Cancer Patients, Stage III with N1; n=32Lung Cancer Patients, Stage III with N2; n=94

Cumulative Proportion Surviving (Kaplan-Meier)Complete Censored

Prediction of Lung Cancer Patients with Stage IIILog-rank Test P=0.0087

Years after Complete Resections

Cum

ulat

ive

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Lung Cancer Patients, Stage III with N1, n=32Lung Cancer Patients, Stage III with N2, n=94

Cumulative Proportion Surviving (Kaplan-Meier)Complete Censored

Prediction of Lung Cancer Patients with Stage III Chi2=17,132; df=2; P=0.0002; n=139

Years after Complete Resections

Cum

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Surgery Alone, n=54P/O Radiotherapy, n=45Adjuvant Chemoimmunoradiotherapy, n=40

Cumulative Proportion Surviving (Kaplan-Meier)Complete Censored

Prediction of Lung Cancer Patients with Stage IIILog-rank Test P=0.0078; n=139

Years after Complete Resections

Cum

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Adjuvant Treatment, n=95Surgery Alone, n=54

Page 15: Kshivets O. Lung Cancer Stage III Surgery

Cumulative Proportion Lung Cancer Patients Surviving (Kaplan-Meier)Cumulative Proportion Surviving (Kaplan-Meier)

Complete CensoredPrediction of Lung Cancer Patients Survival with Stage III

Surgery Alone vs. Adjuvant ChemoimmunoradiotherapyLong-Rank Test P=0.00005; n=94

Years after Complete Resections

Cum

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ive

Prop

ortio

n Su

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Surgery Alone, n=54Adjuvant Chemoimmunoradiotherapy, n=40

Cumulative Proportion Surviving (Kaplan-Meier)Complete Censored

Prediction of Lung Cancer Patient Survival with Stage IIISurgery Alone vs. P/O Radiotherapy

Long-Rank Test P=0.551; n=99

Years after Complete Resections

Cum

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ive

Prop

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Surgery Alone, n=54P/O Radiotherapy, n=45

Cumulative Proportion Surviving (Kaplan-Meier)Complete Censored

Prediction of Lung Cancer Patients Survival with Stage IIIAdjuvant Chemoimmunoradiotherapy vs. P/O Radiotherapy

Long-Rank Test P=0.00116; n=85

Years after Complete Resections

Cum

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Adjuvant Chemoimmunoradiotherapy, n=40P/O Radiotherapy, n=45

Page 16: Kshivets O. Lung Cancer Stage III Surgery

Results of Multivariate

Proportional Hazard Cox Regression

Analysis:

Variables in the Equation

-.528 .296 3.181 1 .075 .590 .330 1.05412.402 2 .002

-.283 .321 .777 1 .378 .753 .401 1.4141.545 .454 11.568 1 .001 4.688 1.924 11.419

6.626 2 .036.877 .374 5.508 1 .019 2.404 1.156 5.000.565 .326 3.006 1 .083 1.760 .929 3.335

7.231 2 .027-.971 .444 4.786 1 .029 .379 .159 .904-.588 .269 4.772 1 .029 .555 .327 .941-.943 .468 4.059 1 .044 .390 .156 .975

-3.142 1.555 4.082 1 .043 .043 .002 .910.016 .005 10.631 1 .001 1.016 1.006 1.026.387 .202 3.682 1 .055 1.473 .992 2.188

-.185 .096 3.695 1 .055 .831 .689 1.004-.248 .106 5.457 1 .019 .780 .634 .961

-16.183 6.926 5.459 1 .019 .000 .000 .074-13.687 6.733 4.132 1 .042 .000 .000 .612

1.323 .424 9.748 1 .002 3.755 1.636 8.6171.970 .646 9.297 1 .002 7.173 2.021 25.451

-11.581 5.270 4.829 1 .028 .000 .000 .286-.011 .008 1.703 1 .192 .989 .973 1.005.146 .040 13.208 1 .000 1.157 1.069 1.251.360 .112 10.293 1 .001 1.433 1.150 1.785.328 .145 5.089 1 .024 1.388 1.044 1.845

-.114 .075 2.331 1 .127 .892 .770 1.033.003 .001 10.703 1 .001 1.003 1.001 1.006

13.279 4 .010-.305 .538 .322 1 .571 .737 .257 2.114-.134 .350 .147 1 .701 .874 .440 1.736

-5.971 1.654 13.030 1 .000 .003 .000 .065.039 .330 .014 1 .906 1.040 .544 1.986

-1.647 .346 22.607 1 .000 .193 .098 .380.691 .367 3.548 1 .060 1.996 .972 4.098

-.018 .006 8.010 1 .005 .983 .971 .995-3.514 1.301 7.289 1 .007 .030 .002 .3823.355 1.342 6.245 1 .012 28.640 2.062 397.8333.699 1.596 5.374 1 .020 40.410 1.771 921.975.184 .120 2.339 1 .126 1.202 .950 1.521

-.209 .075 7.871 1 .005 .811 .701 .9393.449 1.466 5.530 1 .019 31.457 1.776 557.1812.120 1.215 3.043 1 .081 8.332 .769 90.2292.649 1.127 5.521 1 .019 14.144 1.552 128.905

GROWTHHISTHIST(1)HIST(2)GG(1)G(2)N12_0N12_0(1)N12_0(2)ERCITHRSTICKSLYMEABSSTICKABSSABSLYMABSMABST_HEMBILIRTIMFIBR_BFIBRTOL_HEPOPEROPER(1)OPER(2)OPER(3)OPER(4)CHT_IT_RER_CCTHR__CCL_CCS_CCLYM_CCMASS_CCL_TOTE_TOTSTICK_TOTM_TOT

B SE Wald df Sig. Exp(B) Lower Upper95% CI for Exp(B)

Page 17: Kshivets O. Lung Cancer Stage III Surgery

Results of Multifactor Analysis in Prediction of Lung Results of Multifactor Analysis in Prediction of Lung

Cancer Patients Survival with Stage IIIA & IIIB (n=139)Cancer Patients Survival with Stage IIIA & IIIB (n=139) Factor Loadings, Factor 1 vs. Factor 2

Rotation: Varimax normalizedExtraction: Principal components

Prediction of LCP with stage III (n=139)

Factor 1

Fact

or 2 sex

age

weight

grrhloc

grhist G

T

N

D

er

hb

thr

LE

P

S

Lym

M

ESS

Coaghem

glu

PIbil

timsul

prot

recthrTfibrB

fibrhep

LS

Sur5

oper

RT

CHIRTsur

er/cc

thr/cc

L/ccE/cc

P/cc

S/cc

Lym/cc

M/cc

hc/ccStIIIAB

-1.0

-0.6

-0.2

0.2

0.6

1.0

-0.4 -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2

Page 18: Kshivets O. Lung Cancer Stage III Surgery

Results of Discriminant Analysis in Prediction of Lung Cancer Patients Survival with Stage III after Complete Resections (n=131)

Discriminant Function Analysis Summary

Wilks' Lambda: .57124 approx. F (17,113)=4.9890 p< 0.0000Wilks' Partial F-remove Lambda Lambda (1,113) P-level

Ad.CHTITR .651484 .876837 15.87236 .000120PI .597889 .955437 5.27047 .023535N0-2 .615918 .927469 8.83695 .003608M .597130 .956651 5.12045 .025556SUL .579428 .985878 1.61866 .205891BILIRUBIN .603061 .947242 6.29376 .013535FIBR-B .599580 .952742 5.60500 .019609E/CC .583896 .978333 2.50258 .116455HISTOLOGY .578991 .986621 1.53229 .218335HEP.TOL .592369 .964340 4.17857 .043263REC.T. .577855 .988561 1.30758 .255250StageIIIAB .591518 .965728 4.01021 .047620Tumor Size .583061 .979735 2.33731 .129102P/o RT .579747 .985336 1.68174 .197335TIM .580790 .983565 1.88818 .172127GROWTH .580624 .983847 1.85522 .175887LYM .578408 .987616 1.41696 .236398

Page 19: Kshivets O. Lung Cancer Stage III Surgery

Results of Logistic Regression Analysis in Prediction of Lung Cancer Patients Survival with Stage III

after Complete Resections (n=131)

B S.E. Wald df Sig. Exp(B) 95.0% C.I.for EXP(B) P Lower Upper

GROWTH -1.007 .600 2.813 1 .094 .365 .113 1.185N0-2 10.212 2 .006N0-2(1) 5.122 1.933 7.022 1 .008 167.660 3.795 7407.571N0-2(2) 1.824 .716 6.482 1 .011 6.196 1.522 25.226E .223 .130 2.951 1 .086 1.250 .969 1.613S .139 .066 4.471 1 .034 1.149 1.010 1.306M .217 .097 4.999 1 .025 1.243 1.027 1.503SABS 226.039 121.7 3.450 1 .063 1.6E+98 .000 5.8E+201COAG_B -3.767 2.029 3.449 1 .063 .023 .000 1.232PI -.065 .038 2.935 1 .087 .937 .869 1.009BILIRUBIN -.550 .197 7.815 1 .005 .577 .392 .848TIM -1.019 .379 7.240 1 .007 .361 .172 .758FIBR-B -2.152 .896 5.773 1 .016 .116 .020 .673HEP.TOL. -.007 .003 7.733 1 .005 .993 .987 .998AD.CHIRT -2.342 .717 10.671 1 .001 .096 .024 .392L/CC 1.664 .657 6.412 1 .011 5.279 1.456 19.137S/CC -2.664 1.062 6.291 1 .012 .070 .009 .559STIIIAB -3.027 1.612 3.526 1 .060 .048 .002 1.142Constant 8.398 5.561 2.280 1 .131 4436.565

Page 20: Kshivets O. Lung Cancer Stage III Surgery

Results of Clustering in Prediction of Lung

Cancer Patients 5-Year Survival

(n=131)

Page 21: Kshivets O. Lung Cancer Stage III Surgery

Results of Clustering in Prediction of Lung Cancer Patients Survival with Stage III after Complete Resections (n=131)

Logical Formulas based on Simple Mean5YS.Losses: 44.00 <= Weight (5.3%) <= 123.00 &

1.00 <= M (4.8%) <= 13.00 &

74.00 <= PI (7.6%) <= 118.00 & 1.30 <= Sul (6.1%) <= 2.20 & not CHIRT.Grad 2(6.7%) Objects 87 Error1 = 0.16 (14) Error2 = 0.55 (24)

5YS.Survivors:46.00 <= Weight (5.3%) <= 103.00 & 1.00 <= M (4.8%) <= 17.00 & 82.00 <= PI (7.6%) <= 110.00 & 1.60 <= Sul (6.1%) <= 2.30 & CHIRT.Grad 2(6.7%) Objects 44 Error1 = 0.59 (26) Error2 = 0.15 (13)

Logic Formulas based on Median 5YS.Losses: 44.00 <= Weight (6.8%) <= 123.00 & 0.00 <= E (10.8%) <= 10.00 & 3.00 <= Glu (6.0%) <= 7.60 & 1.30 <= Sul (6.1%) <= 2.20 & 0.03 <= M/cc (7.3%) <= 2.90 Objects 87 Error1 = 0.00 (0) Error2 = 0.93 (41)

5YS.Survivors: Growth.Grad 1(11.9%) & also not Growth.Grad 2(11.1%) & 39.00 <= S (4.7%) <= 83.00 & 1.00 <= M (8.1%) <= 17.00 & 82.00 <= PI (10.9%) <= 110.00 Objects 44 Error1 = 0.39 (17) Error2 = 0.37 (32)

Logic Formulas based on Semi-Range 5YS.Losses 170.00 <= Thr (10.7%) <= 681.00 & 1.00 <= M (25.6%) <= 13.00 & 60.00 <= Rec.T. (27.3%) <= 246.00 Objects 87 Error1 = 0.00 (0) Error2 = 0.86 (38)

5YS.Survivors 3.10 <= Er (3.8%) <= 5.10 & 0.80 <= CI (4.0%) <= 1.00 & 0.00 <= P/cc (3.8%) <= 0.44 & 9.98 <= Ertot (3.8%) <= 36.77 & 0.00 <= Ptot (3.8%) <= 2.96 Objects 44 Error1 = 0.00 (0) Error2 = 0.86 (75)

Page 22: Kshivets O. Lung Cancer Stage III Surgery

Results of Results of CorrespondenceCorrespondence Analysis in Prediction of Analysis in Prediction of LungLung Cancer Patients Survival with Stage III (n=131)Cancer Patients Survival with Stage III (n=131)

Page 23: Kshivets O. Lung Cancer Stage III Surgery

Results of Bootstrap Resampling in Prediction of 5-Year Survival of Lung Cancer Patients with Stage III (n=131; subsamplings=935)

Page 24: Kshivets O. Lung Cancer Stage III Surgery

Results of Bootstrap Resampling in Prediction of 5-Year Survival of Lung Cancer Patients with Stage III (n=131; subsamplings=935)

Page 25: Kshivets O. Lung Cancer Stage III Surgery

Results of Bootstrap Simulation in Prediction of Lung Cancer Patients Survival with Stage III after Complete

Resections (n=131; subsamplings=935)

Factor Rank Kendall’s P Tau-A

PI 1 -0.1479 0.00000Mtot 2 0.1474 0.00000Ertot 3 0.1423 0.00000Weight 4 0.1363 0.00000M% 5 0.1344 0.00000M/CC 6 0.1280 0.00000Etot 7 0.1201 0.00000Mabs 8 0.1178 0.00000Sul 9 0.1127 0.00000Ad.CHIRT 10 0.1116 0.00000Surgery Alone 11 -0.10980.00000Eabs 12 0.0997 0.00001N 13 -0.0986 0.00001E% 14 0.0978 0.00001S% 15 -0.0955 0.00001

Factor Rank Kendall’s P Tau-A E/CC 16 0.09510.00002Glucose 17 0.0937 0.00002Er 18 0.09230.00003Growth 19 -0.0898 0.00003Thrtot 20 0.0814 0.0004Tim 21 -0.0770 0.0005Bilirubim 22 -0.0763 0.0005Lymtot 23 0.0759 0.0005T 24 0.0669 0.002ESS 25 -0.0615 0.005Hep.Tol. 26 -0.0577 0.011G 27 -0.0545 0.013Fibrinogen-B 28 -0.0539 0.015D 29 0.0536 0.016Lym% 30 0.0500 0.030Operation 31 -0.0445 0.048

Page 26: Kshivets O. Lung Cancer Stage III Surgery

Results of Neural Networks Computing in Prediction of Lung Cancer Patients Survival with Stage III after

Complete Resections (n=131)

Factor Rank Error RatioAd.CHIRT 1 0.297 107.88G 2 0.242 88.091P/o RT 3 0.212 76.997N 4 0.196 71.221Growth 5 0.171 62.357Histology 6 0.157 57.028Operation 7 0.121 43.899Stage IIIAB8 0.113 41.246M(%) 9 0.089 32.447ESS 10 0.074 26.929PI 11 0.070 25.534T 12 0.058 21.062HC/CC 13 0.052 19.032Eabs 14 0.034 12.239Hep.Tol. 15 0.028 10.040

Factor Rank Error RatioS(%) 16 0.027 9.849E/CC 17 0.025 9.066Surgery Alone 18 0.023 8.537Sex 19 0.010 3.731Lym(%) 20 0.009 3.120Fibrinogen 21 0.008 3.074E(%) 22 0.008 3.046Glucose 23 0.007 2.490Fibrinogen-B 24 0.006 2.201Age 25 0.005 1.756Thr/CC 26 0.005 1.671Hb 27 0.004 1.447M/CC 28 0.004 1.400Hem.T. 29 0.004 1.313Weight 30 0.004 1.305

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Neural Networks in Prediction of Lung Cancer Patients Survival (n=131)Neural Networks in Prediction of Lung Cancer Patients Survival (n=131)

Losses 5-year survivors Baseline Errors=0.000127;Total 87 44 Area under ROC curve=1.000; Correct 87 44 Correct Classification Rate=100%Wrong 0 0Unknown 0 0Losses 87 0Alive 0 44

Genetic Algorithm SelectionUseful for Gr N G Hb E S Lym M ESS Glu PI T/CC E/CC M/CC Surg ATSurvival YesYes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

Training Error Graph (Sum-squared)Prediction of 5-Year Survival of LCP with Stage IIIA & IIIB (n=131)

Network (MLP): Error=0.000127; Area Under ROC Curve=1.00; Correct Classification=1.00

Epoch

Erro

r

0.0

0.2

0.4

0.6

0.8

0 10 20 30 40 50 60

Train by Levenberg-Marquardt, n=131

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Prediction of Lung Cancer Patients Survival with Stage III after Complete Resections (n=131)

Classification of Cases by Logistic Regression, n=131(5-Year Survivors--Losses)

Observed Pred.Losses Pred.Survivors CorrectLosses 76 11 87.4%5-Year Survivors 21 23 52.3%Total 97 34 75.6%Classification of Cases by General Discriminant Analysis, n=131

(5-Year Survivors--Losses)Observed Pred.Losses Pred.Survivors CorrectLosses 79 8 90.8%5-Year Survivors 11 33 75.0%Total 90 41 85.5%

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Prediction of Lung Cancer Patients Survival with Stage III after Complete Resections (n=131)

Classification of Cases by Clastering, n=131(5-Year Survivors--Losses)

Observed Pred.Losses Pred.Survivors CorrectLosses 81 6 93.1%5-Year Survivors 9 35 79.5%Total 90 41 88.5%

Classification of Cases by Neural Networks, n=131(5-Year Survivors--Losses)

Observed Pred.Losses Pred.Survivors CorrectLosses 87 0 100.0%5-Year Survivors 0 44 100.0%Total 87 44 100.0%

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Lymphocyte Lymphocyte & & Monocyte Monocyte Circuit in Circuit in Prediction Prediction of Lung Cancer of Lung Cancer Patients Patients

Survival Survival with Stage III (n=131) with Stage III (n=131)

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Ratio of Segmented Neutrophile and Cancer Cell Ratio of Segmented Neutrophile and Cancer Cell Populations Populations & & Blood Glucose Level Blood Glucose Level in in Prediction Prediction of Lung of Lung

Cancer Cancer Patients Survival with Stage IIIPatients Survival with Stage III (n=131) (n=131)

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Weight Weight & & Prothrombin Index Prothrombin Index in in Prediction Prediction of Lung of Lung Cancer Cancer Patients Survival with Stage IIIPatients Survival with Stage III (n=131) (n=131)

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Significant Networks between Clinicopathologic, Biochemic, Hemostasis & Hematologic Significant Networks between Clinicopathologic, Biochemic, Hemostasis & Hematologic Data and 5-Year Survival of Lung cancer Patients with Stage III (n=131)Data and 5-Year Survival of Lung cancer Patients with Stage III (n=131)

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Results of Monte Carlo Simulation in Prediction of Lung Cancer Results of Monte Carlo Simulation in Prediction of Lung Cancer Patients Survival with Stage III (n=131)Patients Survival with Stage III (n=131)

-0.25 0.109 0.468 0.828 1.187 1.546 1.905 2.264 2.623 2.983 above

Results of Monte Carlo SimulationPrediction of Lung Cancer Patients Survival with Stage III, n=131

P=0.000000

-1.66 -1.38 -1.1 -0.821 -0.541 -0.261 0.018 0.298 0.578 0.858 above

Results of Monte Carlo SimulationPrediction of 5-Year Survival of Lung Cancer Patients with Stage III, n=131

P=0.002

-1.319 -0.887 -0.455 -0.023 0.409 0.841 1.273 1.704 2.136 2.568 above

Results of Monte Carlo SimulationPrediction of Lung Cancer Patients Survival with Stage III, n=131

P=0.000000

-1.322 -1.065 -0.807 -0.549 -0.291 -0.034 0.224 0.482 0.739 0.997 above

Results of Monte Carlo SimulationPrediction of Lung Cancer Patients Survival with Stage III, n=131

P=0.000000

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SEPATH Networks in Prediction of Lung Cancer SEPATH Networks in Prediction of Lung Cancer Patients Survival with Stage III (n=131)Patients Survival with Stage III (n=131)

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Holling-Tenner Models of Alive Supersystem “Lung Cancer-Cytotoxic Cell Holling-Tenner Models of Alive Supersystem “Lung Cancer-Cytotoxic Cell PopulationPopulation”

0.01 0.1 1 100.1

1

10

Early Lung CancerLC with T1-2N0M0LC with T1-3N0-1M0LC with T1-4N2M0

Model "Cancer Dynamics--Cytotoxic Cells"

Lung Cancer Cell Population

Cyt

ooto

xic

Cel

l Pop

ulat

ions X1 3

X2 3

X3 3

X4 3

X1 2 X2 2

X3 2 X4 2

0.1 1 10 1000.1

1

10

LC with T1-3N0-1M0LC with T1-4N2M1

Model "Distant MTS---Cytotoxic K-cells"

Time

Cel

l Pop

ulat

ion

Dyn

amic

s

X4 2

X4 3

X4 1

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Lung Cancer Dynamics

Page 38: Kshivets O. Lung Cancer Stage III Surgery

SUPERONCOPROGNOSIS-1.0

PROGNOSIS SURVIVAL-2

PROG-1 PROG-2 PROG-3 E

SURVIVAL LESS 5 YEARS SURVIVAL MORE 5 YEARS

SURVIVAL-1

A B

C

Page 39: Kshivets O. Lung Cancer Stage III Surgery

Conclusions:Conclusions:It was revealed that 5-year survival of lung cancer patients with stage III after complete pulmonary resections significantly depended on: 1) lung cancer characteristics;2) adjuvant treatment; 3) level of blood cell circuit; 4) cell ratio factors; 5) hemostasis system; 6) biochemic homeostasis.

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Address:

Oleg Kshivets, M.D., Ph.D. Thoracic Surgeon Department of Surgery Siauliai Cancer CenterTilzes:42-16, 5400 Siauliai, LithuaniaTel. (37041)[email protected] http//:myprofile.cos.com/Kshivets