This study analyzed data from 665 lung cancer patients who underwent lobectomy or pneumonectomy surgery between 1985-2015. The study aimed to determine factors that predict 5-year survival rates after surgery. Multivariate analysis found that 5-year survival significantly depended on tumor characteristics, blood cell levels, ratios of blood cells to cancer cells, coagulation factors, and use of adjuvant therapy for patients with lymph node involvement. Neural networks analysis correctly predicted 100% of 5-year survival outcomes based on these factors, particularly lymph node involvement, cancer invasiveness, and lymphocyte levels.

1. Oleg Kshivets , MD, PhD
Surgery Department, Kaluga Cancer Clinical Center, Russia
PRECISE PREDICTION OF 5-YEAR
SURVIVAL OF LUNG CANCER PATIENTS
AFTER RADICAL SURGERY

2. ABSTRACT
Precise Prediction of 5-Year Survival of Lung Cancer Patients after Radical Surgery
Oleg Kshivets
OBJECTIVE: This study aimed to determine homeostasis and tumor factors for 5-year survival (5YS) of non-
small cell lung cancer (LC) patients (LCP) (T1-4N0-2M0) after complete en block (R0)
lobectomies/pneumonectomies (LP).
METHODS: We analyzed data of 665 consecutive LCP (age=57.5±8.3 years; tumor size=4.4±2.4 cm) radically
operated and monitored in 1985-2015 (m=575, f=90; lobectomies=423, pneumonectomies=242, combined LP with
resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=180;
only surgery-S=524, adjuvant chemoimmunoradiotherapy-AT=141: CAV/gemzar + cisplatin + thymalin/taktivin +
radiotherapy 45-50Gy; T1=237, T2=248, T3=125, T4=55; N0=419, N1=130, N2=116, M0=665; G1=163, G2=199,
G3=303; squamous=377, adenocarcinoma=243, large cell=45; early LC=132, invasive LC=533. 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 2114.8±1685 days and cumulative 5YS reached 69.6%, 10 years – 61.2%,
20 years – 43.1%. 416 LCP lived more than 5 years without cancer (LS=3041.4±1472.5 days). 193 LCP died because
of LC (LS=559.6±373.5 days). AT significantly improved 5YS (65.1% vs. 34.3%) (P=0.00001 by log-rank test) only
for LCP with N1-2. Cox modeling displayed (Chi2=290.78, df=13, P=0.000) that 5YS of LCP significantly depended
on: phase transition (PT)“early-invasive LC”, 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=0.000-0.035). Neural networks, genetic algorithm selection and bootstrap simulation revealed
relationships between 5YS and PT N0-N12 (rank=1), PT “early-invasive LC” (rank=2), lymphocytes (3), segmented
neutrophils (4), tumor size (5), AT (6), T1-4 (7), ESS (8), prothrombin index (9), glucose (10), thrombocytes/CC (11),
healthy cells/CC (12), lymphocytes/CC (13), erythrocytes/CC (14). Correct prediction of 5YS was 100% by neural
networks computing (error=0.000; area under ROC curve=1.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: tumor characteristics, blood cell
circuit, cell ratio factors, hemostasis system and AT.

3. Data:
 Males………………………………………………….575
 Females………..………………………………….........90
 Age=57.5±8.3 years
 Tumor Size=4.4±2.4 cm
 Only Surgery.………………………………………...524
 Adjuvant Chemoimmunoradiotherapy
 (CAV/gemzar+ cisplatin+thymalin/taktivin, 5-6 cycles+
Radiotherapy 45-50Gy)……………………………...141

4. Radical Procedures::
 Pneumonectomies (R0)……..………………………...242
 Lobectomies (R0)………….………………………….423
 Combined Pneumonectomies/Lobectomies with
Resection of Trachea, Carina, Atrium, Aorta, Vena
 Cava Superior, Vena Azygos, Diaphragm, Pericardium,
Esophagus, Liver, Ribs (R0)………………………....180
 N1 Lymph Node Dissection………………………..…132
 Mediastinal Lymph Node Dissection……………..….533

5. Staging:
 T1……237 N0..….419 G1…………163
 T2……248 N1…...130 G2…………199
 T3……125 N2…...116 G3…………303
 T4……..55 M0…..665
 Adenocarcinoma…………………………….243
 Squamos Cell Carcinoma…………………...377
 Large Cell Carcinoma.……………………….45
 Early Cancer…………………………………132
 Invasive Cancer……………………………...533

6. Survival Rate:
 Alive………………………………………....434 (65.3%)
 5-Year Survivors…………..………………...416 (62.6%)
 10-Year Survivors…………………………...108 (16.2%)
 Losses………………………………………..193 (29%)
 General Life Span=2114.8±1685 days
 For 5-Year Survivors=3041.4±1472.5 days
 For 10-Year Survivors=5053.8±1477.2 days
 For Losses=559.6±373.5 days
 Cumulative 5-Year Survival………………..69.6%
 Cumulative 10-Year Survival………………61.2%
 Cumulative 20-Year Survival………………43.1%

7. General Lung Cancer Patients Survival after Complete
Lobectomies/Pneumonectomies (Kaplan-Meier) (n=665):

8. Results of Univariate Analysis of Phase Transition
Early—Invasive Cancer in Prediction of Lung Cancer
Patients Survival (n=665)

9. Results of Univariate Analysis of Phase Transition N0—N1-2 in
Prediction of Lung Cancer Patients Survival (n=665):

10. Results of Univariate Analysis of Adjuvant
chemoimmunoradioTherapy in Prediction of Lung
Cancer Patients Survival with N1-2 (n=246):

11. Results of Cox Regression Modeling in Prediction of Lung Cancer Patients
Survival after Complete Lobectomies/Pneumonectomies (n=665):
Cox Proportional Hazard Results: Chi² = 290.777 df = 13 p = 0.0000; n=665
Factors:
Parameter
Estimate
Standard
Error Chi² P
95%
Lower CL
95%
Upper CL
Hazard
Ratio
95% Hazard
Ratio Lower CL
95% Hazard
Ratio Upper CL
Histology 0.28729 0.088150 10.62140 0.001118 0.11451 0.460058 1.332806 1.121329 1.584165
G1-3 0.33416 0.090194 13.72639 0.000211 0.15738 0.510939 1.396769 1.170445 1.666855
Phase Transition Early-Invasive Cancer -1.30081 0.393540 10.92567 0.000948 -2.07213 -0.529483 0.272312 0.125917 0.588909
Adjuvant Chemoimmunoradiotherapy -1.00123 0.201243 24.75293 0.000001 -1.39566 -0.606803 0.367426 0.247669 0.545091
Phase Transition N0---N12 1.07094 0.148805 51.79528 0.000000 0.77928 1.362588 2.918108 2.179908 3.906291
Glucose -0.28464 0.081338 12.24633 0.000466 -0.44406 -0.125221 0.752285 0.641427 0.882302
Prothrombin Index 0.03035 0.006847 19.65302 0.000009 0.01693 0.043773 1.030819 1.017078 1.044746
Recalcification Time -0.00599 0.001786 11.24486 0.000798 -0.00949 -0.002488 0.994030 0.990557 0.997515
Heparin Tolerance 0.00366 0.000669 29.84859 0.000000 0.00234 0.004967 1.003662 1.002347 1.004979
Eosinophils/Cancer Cells -1.01650 0.430309 5.58024 0.018164 -1.85989 -0.173108 0.361860 0.155690 0.841046
Lymphocytes/Cancer Cells -0.17837 0.067674 6.94706 0.008396 -0.31101 -0.045732 0.836633 0.732707 0.955298
Erythrocytes tot -0.03776 0.017929 4.43498 0.035210 -0.07290 -0.002617 0.962947 0.929696 0.997386
Thrombocytes tot 0.00049 0.000192 6.45838 0.011043 0.00011 0.000863 1.000487 1.000111 1.000863

12. Results of Neural Networks Computing in Prediction of Lung
Cancer Patients Survival after Complete
Lobectomies/Pneumonectomies (n=609):
Factor Rank Sensitivity
Phase Transition N0---N12 1 4552
Phase Transition Early---Invasive Cancer 2 2430
Lymphocytes 3 2182
Segmented Neutrophils 4 2109
Tumor Size 5 1551
Adjuvant Chemoimmunoradiotherapy 6 1483
T1-4 7 1478
ESS 8 1209
Prothrombin Index 9 1107
Glucose 10 999
Thrombocytes/Cancer Cells 11 906
Healthy Cells/Cancer Cells 12 624
Lymphocytes/Cancer Cells 13 509
Erythrocytes/Cancer Cells 14 404
Corect Classification Rate=100%
Error=0.000
Area under ROC Curve=1.000

13. Results of Bootstrap Simulation in Prediction of Lung Cancer Patients
Survival after Complete Lobectomies/Pneumonectomies (n=609):
Significant Factors (Number of Samples=3333) Rank Kendal Tau-A P
Phase Transition N0---N12 1 -0.215 0.000
Lymphocytes/Cancer Cells 2 -0.206 0.000
Healthy Cells/Cancer Cells 3 -0.203 0.000
Erythrocytes/Cancer Cells 4 -0.202 0.000
Thrombocytes/Cancer Cells 5 -0.176 0.000
Leucocytes/Cancer Cells 6 -0.168 0.000
Prothrombin Index 7 0.162 0.000
Tumor Size 8 -0.144 0.000
Eosinophils/Cancer Cells 9 -0.140 0.000
Phase Transition Early---Invasive Cancer 10 -0.131 0.000
T1-4 11 0.126 0.000
Monocytes/Cancer Cells 12 -0.125 0.000
Segmented Neutrophils/Cancer Cells 13 -0.115 0.000
Segmented Neutrophils 14 0.107 0.000
Weight 15 -0.104 0.000
Lymphocytes 16 -0.102 0.000
Erythrocytes 17 -0.098 0.001
ESS 18 0.084 0.01
G1-3 19 -0.082 0.01
Heparin Tolerance 20 0.077 0.01
Glucose 21 -0.071 0.01
Surgery alone 22 -0.066 0.01
Eosinophils 23 -0.062 0.05

14. Results of Kohonen Self-Organizing Neural Networks
Computing in Prediction of Lung Cancer Patients Survival
after Complete Lobectomies/Pneumonectomies (n=609):

15. Lung Cancer Dynamics:

16. Prognostic SEPATH-Model of Lung Cancer Patients Survival after
Complete Lobectomies/Pneumonectomies (n=609):

17. Address:
Oleg Kshivets, M.D.,Ph.D.
Consultant Thoracic, Abdominal,
General Surgeon & Surgical
Oncologist
 e-mail: okshivets@yahoo.com
 skype: okshivets
 http: //www.ctsnet.org/home/okshivets