1. SURVIVAL OF LUNG CANCER PATIENTS
AFTER LOBECTOMIES WAS SIGNIFICANTLY
SUPERIOR IN COMPARISON WITH LUNG
CANCER PATIENTS AFTER
PNEUMONECTOMIES
Kshivets Oleg, MD, PhD
Surgery Department, Roshal Hospital, Roshal,
Moscow, Russia

2. ABSTRACT
OBJECTIVE: This study aimed to determine surgery type influence for 5-year survival (5YS) of non-small cell lung cancer (LC) patients (LCP) after complete en
block (R0) lobectomies and pneumonectomies.
METHODS: We analyzed data of 765 consecutive patients (age=57.6±8.3 years; tumor size=4.1±2.4 cm) radically operated (R0) and monitored in 1985-2022
(m=659, f=106; bi/lobectomies=512, pneumonectomies=253, mediastinal lymph node dissection=765; combined procedures with resection of trachea, carina,
atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=192; only surgery-S=616, adjuvant chemoimmunoradiotherapy-AT=149:
CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=318, T2=255, T3=133, T4=59; N0=514, N1=131, N2=120, M0=765; G1=194, G2=241, G3=330;
squamous=417, adenocarcinoma=298, large cell=50; early LC=212, invasive LC=553. Multivariate Cox modeling, discriminant analysis, clustering, SEPATH, Monte
Carlo, bootstrap and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 2240.1±1751.6 days and cumulative 5-year survival (5YS) reached 72.8%, 10 years – 64.2%, 20 years – 42.9%. 499 LCP lived
more than 5 years (LS=3126.8±1540 days), 143 LCP – more than 10 years (LS=5083.3±1518.6 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP
after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (77.6% vs.63.1%, P=0.00001 by log-rank test). AT significantly
improved 5YS (64.4% vs. 34.8%) (P=0.00003 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase
transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3,
histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). 5YS of LCP after lobectomies (77.6%) was
significantly superior in comparison with LCP after pneumonectomies (63%) (P=0.00001 by log-rank test). Neural networks, genetic algorithm selection and
bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12(rank=2), thrombocytes/CC (3), erythrocytes/CC (4),
eosinophils/CC (5), healthy cells/CC (6), segmented neutrophils/CC (7), lymphocytes/CC (8), monocytes/CC (9); stick neutrophils/CC (10), leucocytes/CC (11).
Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell
circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) surgery type: lobectomy/pneumonectomy; 10) anthropometric data.

3. RADICAL PROCEDURES:
Bi/Lobectomies (R0)……………………………………..…….…….512
Pneumonectomies (R0)………………….………...........................253
Combined Procedures with Resection of Trachea, Carina,
Atrium, Aorta, VCS, Vena Azygos, Pericardium, Liver,
Diaphragm, Ribs, Esophagus (R0)……………...........................192
Mediastinal Lymphadenectomy………………………..………….765

4. DATA:
Males……………………………………………………………….....659
Females………..……………………………………….…................106
Age=57.6±8.3 years
Tumor Size=4.1±2.1 cm
Only Surgery.……………………………………………….............616
Adjuvant Chemoimmunoradiotherapy
(CAV/gemzar+cisplatin+thymalin/taktivin, 5-6 cycles+
Radiotherapy 45-50Gy)…………................................................149

5. STAGING:
T1……318 N0..….514 G1…………194
T2……255 N1…...131 G2…………241
T3……133 N2…...120 G3…………330
T4……..59 M0…..765
Adenocarcinoma………………………….….417
Squamos Cell Carcinoma…………………..228
Large Cell Carcinoma…………………...........50
Early Cancer……………………………...…...212
Invasive Cancer…………………………..…..553 .

6. SURVIVAL RATE:
Alive……………………………………….....511 (66.8%)
5-Year Survivors…………..……………….499 (65.2%)
10-Year Survivors………………………….143 (18.7%)
Losses……………………………………….199 (26%)
General Life Span=2240.1±1751.6 days
For 5-Year Survivors=3126.8±1540 days
For 10-Year Survivors=5083.3±1518.6 days
For Losses=562.7±374.5 days
Cumulative 5-Year Survival……………………..72.8%
Cumulative 10-Year Survival…………………....64.2%
Cumulative 20-Year Survival…………………....42.9%

7. GENERAL LUNG CANCER PATIENTS SURVIVAL AFTER COMPLETE
LOBECTOMIES/PNEUMONECTOMIES (KAPLAN-MEIER) (N=765):
Survival Function
5YS of LCP=72.8%; 10YS=64.2%; 20YS=42.9%.
Complete Censored
-5 0 5 10 15 20 25 30
Years after Surgery
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving

8. RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION EARLY—INVASIVE
CANCER IN PREDICTION OF LUNG CANCER PATIENTS SURVIVAL (N=765):
Cumulative Proportion Surviving (Kaplan-Meier)
5YS LCP with Early Cancer=100%; 5YS LCP with Invasive Cancer=62%;
P=0.0000 by Log-Rank Test.
Complete Censored
0 5 10 15 20 25 30 35
Years after Surgery
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative
Proportion
Surviving
LCP with Invasive Cancer
LCP with Early Cancer

9. RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION N0—N1-2
IN PREDICTION OF LUNG CANCER PATIENTS SURVIVAL (N=765):
Cumulative Proportion Surviving (Kaplan-Meier)
5YS LCP with N0=86.8%; 5YS LCP with N12=43.4%;
P=0.0000 by Log-Rank Test.
Complete Censored
0 5 10 15 20 25 30 35
Years after Surgery
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
LCP with N12
LCP with N0

10. RESULTS OF UNIVARIATE ANALYSIS OF ADJUVANT
CHEMOIMMUNORADIOTHERAPY IN PREDICTION OF LUNG CANCER PATIENTS
SURVIVAL WITH N1-2 (N=251):
Cumulative Proportion Surviving (Kaplan-Meier)
LCP with N12 5YS LCP after Adjuvant Treatment=63.4%; 5YS after surgery along=34.8%;
P=0.00003 by Log-Rank Test.
Complete Censored
0 5 10 15 20 25 30
Years after Surgery
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
only Surgery
Adjuvant Chemoimmunoradiotherapy

11. RESULTS OF UNIVARIATE ANALYSIS OF SURGERY TYPE (LOBECTOMIES VS.
PNEUMONECTOMIES) IN PREDICTION OF LUNG CANCER PATIENTS SURVIVAL (N=765):
Cumulative Proportion Surviving (Kaplan-Meier)
5YS LCP after Lobectomies=77.6%; 5YS LCP after Pneumonectomies=63%;
P=0.00001 by Log-Rank Test.
Complete Censored
0 5 10 15 20 25 30 35
Years after Surgery
-0.1
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
LCP after Pneumonectomies
LCP after Lobectomies

12. RESULTS OF COX REGRESSION MODELING IN PREDICTION OF LUNG CANCER
PATIENTS SURVIVAL AFTER COMPLETE SURGERY (N=756):
Cox
Parameter
Estimate
Standard
Error
Chi-
square
P value
95%
Lower CL
95%
Upper CL
Hazard
Ratio
PT N0----N12 1.12860 0.144710 60.82492 0.000000 0.84497 1.4122293.091330
PT Early-Invasive LC -1.47064 0.289169 25.86488 0.000000 -2.03740 -0.9038810.229778
Histology 0.32311 0.083065 15.13080 0.000100 0.16030 0.4859111.381414
Heparin Tolerance 0.00334 0.000653 26.16087 0.000000 0.00206 0.0046221.003347
Recalcification Time -0.00395 0.001693 5.43911 0.019691 -0.00727 -0.0006300.996059
Prothrombin Index 0.03107 0.006560 22.43073 0.000002 0.01821 0.0439241.031555
AT -1.03805 0.196916 27.78926 0.000000 -1.42400 -0.6521060.354143
Leucocytes/CC -0.40957 0.150122 7.44318 0.006368 -0.70380 -0.1153320.663939
Segmented Neut/CC 0.43089 0.162072 7.06844 0.007845 0.11324 0.7485501.538633
Lymphocytes/CC 0.37542 0.172624 4.72960 0.029648 0.03708 0.7137521.455597
G1-3 0.31333 0.087560 12.80502 0.000346 0.14171 0.4849431.367969
Glucose -0.32171 0.077069 17.42452 0.000030 -0.47276 -0.1706540.724911
Thrombocytes tot 0.00055 0.000184 8.94820 0.002777 0.00019 0.0009131.000552
Erythrocytes tot -0.03595 0.016873 4.53860 0.033139 -0.06902 -0.0028760.964691
Age 0.01723 0.008588 4.02430 0.044849 0.00040 0.0340601.017377

13. RESULTS OF NEURAL NETWORKS COMPUTING IN PREDICTION OF LUNG
CANCER PATIENTS SURVIVAL AFTER COMPLETE SURGERY (N=698):
Corect Classification Rate=100%;
Error=0.000;
Area under ROC Curve=1.000.
Factors, LCP=698 Rank Sensitivity
Phase Transition Early—Invasive Cancer 1 28854
Phase Transition N0---N12 2 25420
Thrombocytes/Cancer Cells 3 11601
Erythrocytes/Cancer Cells 4 11414
Eosinophils/Cancer Cells 5 10658
Healthy Cells/Cancer Cells 6 8871
Segmented Neutrophils/Cancer Cells 7 7844
Lymphocytes/Cancer Cells 8 6416
Monocytes/Cancer Cells 9 5454
Stick Neutrophils/Cancer Cells 10 5353
Leucocytes/Cancer Cells 11 4075

14. RESULTS OF BOOTSTRAP SIMULATION IN PREDICTION OF
LUNG CANCER PATIENTS SURVIVAL AFTER SURGERY (N=698):
Bootstrap Simulation n=698
Significant Factors
(Number of Samples=3333)
Rank Kendal
Tau-A
P<
Healthy Cells/Cancer Cells 1 -0.297 0.000
Erythrocytes/Cancer Cells 2 -0.293 0.000
Lymphocytes/Cancer Cells 3 -0.287 0.000
Thrombocytes/Cancer Cells 4 -0.268 0.000
Leucocytes/Cancer Cells 5 -0.258 0.000
Segmented Neutrophils/Cancer Cells 6 -0.208 0.000
Tumor Size 7 0.174 0.000
Phase Transition Early-Invasive Cancer 8 -0.163 0.000
Phase Transition N0---N12 9 -0.158 0.000
T1-4 10 0.151 0.000
Prothrombin Index 11 0.141 0.000
Lymphocytes tot 12 -0.140 0.000
Erythrocytes tot 13 -0.138 0.000
Monocytes/Cancer Cells 14 -0.115 0.000
Segmented Neutrophils% 15 0.102 0.000
G1-3 16 0.090 0.001
Lymphocytes% 17 -0.089 0.001
Weight 18 -0.088 0.001
ESS 19 0.086 0.01
Pneumonectomies/Lobectomies 20 -0.067 0.01
Glucose 21 -0.060 0.05
Heparin Tolerance 22 0.060 0.05
Eosinophils/Cancer Cells 23 -0.060 0.05
Eosinophils% 24 -0.055 0.05

15. RESULTS OF KOHONEN SELF-ORGANIZING NEURAL NETWORKS COMPUTING IN
PREDICTION OF LUNG CANCER PATIENTS SURVIVAL AFTER SURGERY (N=698):

16. LUNG CANCER DYNAMICS:

17. PROGNOSTIC SEPATH-MODEL OF LUNG CANCER
PATIENTS SURVIVAL AFTER SURGERY (N=698):

18. 5YS OF LCP AFTER RADICAL
PROCEDURES SIGNIFICANTLY
DEPENDED ON:
1) PHASE TRANSITION EARLY-INVASIVE
CANCER;
2) PHASE TRANSITION N0--N12;
3) CELL RATIO FACTORS;
4) BLOOD CELL CIRCUIT;
5) BIOCHEMICAL FACTORS;
6) HEMOSTASIS SYSTEM;
7) ADJUVANT TREATMENT;
8) LC CHARACTERISTICS;
9) SURGERY TYPE:
LOBECTOMY/PNEUMONECTOMY;
10) ANTHROPOMETRIC DATA.
Conclusion:

19. 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