Lung Cancer Prognosis and Cell Ratio Factors OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting non-small cell lung cancer (LC) patients (LCP) survival. CRF - ratio between cancer cells (CC) and blood cells subpopulations. Cox modeling displayed that LCP survival significantly depended on CRF: leucocytes/CC, segmented neutrophils/CC, lymphocytes/CC, healthy cells/CC (P=0.000-0.016). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and healthy cells/CC (rank=1), segmented neutrophils/CC (rank=2), erythrocytes/CC (rank=3), thrombocytes/CC (4), leucocytes/CC (5), lymphocytes/CC (6), eosinophils/CC (7), monocytes/CC (8), stick neutrophils/CC (9). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0). CONCLUSIONS: LCP survival after radical procedures significantly depended on CRF.

1. Lung Cancer Prognosis and Cell
Ratio Factors
Kshivets Oleg
Roshal Hospital, Roshal, Moscow
Russia

2. Presenter DISCLOSURES
Ineligible Company
(formerly: Commercial Interest)
Relationship(s)
No No

3. Abstract
Lung Cancer Prognosis and Cell Ratio Factors
Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia
OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting non-small cell lung cancer (LC) patients (LCP) survival. CRF - ratio
between cancer cells (CC) and blood cells subpopulations.
METHODS: We analyzed data of 768 consecutive LCP (T1-4N0-2M0) (age=57.6±8.3 years; tumor size=4.1±2.4 cm) radically operated (R0) and
monitored in 1985-2021 (m=660, f=108; upper lobectomies=277, lower lobectomies=177, middle lobectomies=18, bilobectomies=42,
pneumonectomies=254, mediastinal lymph node dissection=768; combined procedures with resection of trachea, carina, atrium, aorta, VCS, vena
azygos, pericardium, liver, diaphragm, ribs, esophagus=193; only surgery-S=618, adjuvant chemoimmunoradiotherapy-AT=150: CAV/gemzar +
cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=320, T2=255, T3=133, T4=60; N0=516, N1=131, N2=121, M0=768; G1=194, G2=243,
G3=331; squamous=417, adenocarcinoma=301, large cell=50; right LC=412, left LC=356; central=290; peripheral=478. Variables selected for
prognosis study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier
method. Differences in curves between groups of LCP were evaluated using a log-rank test. 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 2244.9±1750.3 days and cumulative 5-year survival (5YS) reached 72.9%, 10 years – 64.3%, 20 years –
43.1%. 502 LCP lived more than 5 years (LS=3128.7±1536.8 days), 145 LCP – more than 10 years (LS=5068.5±1513.2 days).199 LCP died because
of LC (LS=562.7±374.5 days). Cox modeling displayed that LCP survival significantly depended on CRF: leucocytes/CC, segmented neutrophils/CC,
lymphocytes/CC, healthy cells/CC (P=0.000-0.016). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships
between 5YS and healthy cells/CC (rank=1), segmented neutrophils/CC (rank=2), erythrocytes/CC (rank=3), thrombocytes/CC (4), leucocytes/CC (5),
lymphocytes/CC (6), eosinophils/CC (7), monocytes/CC (8), stick neutrophils/CC (9). Correct prediction of 5YS was 100% by neural networks
computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: LCP survival after radical procedures significantly depended on CRF.

4. Data:
Males……………………………………..…….….660
Females…….....................................................108
Age=57.6±8.3 years Tumor Size=4.1±2.4 cm
Only Surgery.…................................................618
Adjuvant Chemoimmunoradiotherapy
(CAV/gemzar + cisplatin + thymalin/taktivin, 5-6
cycles+ Radiotherapy 45-50Gy)......................150

5. Radical Procedures (R0):
Upper Lobectomies……….………………………………...277
Lower Lobectomies.….....................................................177
Middle Lobectomies.…………………………..…………….18
Bilobectomies.………………………………..……………....42
Pneumonectomies……………………………..……………254
Combined Procedures with Resection of Trachea, Carina,
Atrium, Aorta, Vena Cava Superior, Vena Azygos,
Pericardium, Liver, Diaphragm, Ribs, Esophagus…….193
Mediastinal Lymphadenectomy.………………..…...……768

6. Staging:
T1……..320 N0..……516 G1…………194
T2……..255 N1…......131 G2…………243
T3……..133 N2…......121 G3…………331
T4………60 N1-2…...252 M0…….…...768
Adenocarcinoma………………………………………………………..301
Squamous Cell Carcinoma……………………………………..……..417
Large Cell Carcinoma………………………………………..................50

7. Survival Rate:
5-Year Survivors…………......................................................502 (65.4%)
10-Year Survivors……………………………………................145 (18.9%)
Losses……………………………………………………………..199 (25.9%)
General Life Span=2244.9±1750.3 days
For 5-Year Survivors=3128.7±1536.8 days
For 10-Year Survivors=5068.5±1513.2 days
For Losses=562.7±374.5 days
Cumulative 5-Year Survival……..……….........................................72.9%
Cumulative 10-Year Survival……..…...……………………………...64.3%
Cumulative 20-Year Survival………………………………………....43.1%

8. Survival Function
5-Year Survival=72.9%; 10-Year survival=64.3%; 20-Year Survival=43.1%;
n=768; T1-4N0-2M0
Complete Censored
-5 0 5 10 15 20 25 30
Years after Lobectomies/Pneumonectomies
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
General Lung Cancer Patients Survival after Complete
Lobectomies/Pneumonectomies (Kaplan-Meier) (n=768):

9. Cumulative Proportion Surviving (Kaplan-Meier)
10-Year Survival of Early Lung Cancer Patients=93.9%;
10-Year Surival of Invasive Lung Cancer Patients=51.8%;
P=0.0000 by Log Rank Test
Complete Censored
0 5 10 15 20 25 30 35
Years after Lobectomies/Pneumonectomies
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
Cumulative
Proportion
Surviving
Invasive Lung Cancer, n=554
Early Lung Cancer, n=214
Results of Univariate Analysis of Phase Transition Early—Invasive
Cancer in Prediction of Lung Cancer Patients Survival (n=768):

10. Cumulative Proportion Surviving (Kaplan-Meier)
10-Year Survival of Lung Cancer Patients with N0=78.3%;
10-Year Survival of Lung Cancer Patients with N1-2=35.2%;
P=0.0000 by Log Rank Test
Complete Censored
0 5 10 15 20 25 30 35
Years After Lobectomies/Pneumonectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
Lung Cancer with N1-2, n=252
Lung Cancer with N0=516
Results of Univariate Analysis of Phase Transition N0—N1-2 in
Prediction of Lung Cancer Patients Survival (n=768):

11. Results of Cox Regression Modeling in Prediction of Lung Cancer
Patients Survival after Complete Lobectomies/Pneumonectomies
(n=768):
Cell Ratio Factors, n=768
Parameter
Estimate
Standard
Error
Chi-
square
P value
95%
Lower CL
95%
Upper CL
Hazard
Ratio
Leucocytes/CC -0.476505 0.139217 11.71515 0.000620 -0.749366 -0.203644 0.620950
Segmented Neutrophils/CC 0.533254 0.151376 12.40947 0.000427 0.236562 0.829946 1.704470
Lymphocytes/CC 0.395129 0.164461 5.77231 0.016281 0.072791 0.717467 1.484576
Healthy Cells/CC -0.039992 0.009692 17.02492 0.000037 -0.058988 -0.020995 0.960797

12. Results of Discriminant Function Analysis in Prediction of Lung Cancer Patients
Survival after Complete Lobectomies/Pneumonectomies (n=701):
N=701
Discriminant Function Analysis Summary: No. of vars in
model: 4; Grouping: SUR5 (2 grps) Wilks' Lambda: .73129
approx. F (4,696)=63.935 p<0.0000
Wilks'
Lambda
Partial
Lambda
F-remove
(1,696)
p-value Toler.
1-Toler.
(R-Sqr.)
PT N0----N12 0.834783 0.876027 98.49628 0.000000 0.896934 0.103066
Leucocytes/Cancer Cells 0.736380 0.993091 4.84203 0.028102 0.082118 0.917882
Segmented Neutrophils/Cancer Cells 0.735348 0.994484 3.86025 0.049840 0.083382 0.916618
PT Early---Invasive Cancer 0.759831 0.962441 27.16153 0.000000 0.696661 0.303340
N=701
Discriminant Function Analysis Summary: No. of vars in
model: 6; Grouping: SUR5 (2 grps) Wilks' Lambda: .88304
approx. F (6,694)=15.320 p< .0000
Wilks'
Lambda
Partial
Lambda
F-remove
(1,694)
p-value Toler.
1-Toler.
(R-Sqr.)
Erythrocytes/Cancer Cells 0.918245 0.961665 27.66516 0.000000 0.347042 0.652958
Leucocytes/Cancer Cells 0.897282 0.984132 11.19023 0.000867 0.000938 0.999062
Stick Neutrophils/Cancer Cells 0.889808 0.992398 5.31623 0.021422 0.306522 0.693478
Segmented Neutrophils/Cancer Cells 0.898416 0.982890 12.08124 0.000541 0.002170 0.997830
Lymphocytes/Cancer Cells 0.895310 0.986299 9.64051 0.001981 0.007649 0.992351
Monocytes/Cancer Cells 0.894198 0.987525 8.76678 0.003172 0.111689 0.888311

13. Results of Neural Networks Computing in Prediction of Lung Cancer
Patients Survival after Complete Lobectomies/Pneumonectomies
(n=701):
Neural Networks: n=701;
Baseline Error=0.000;
Area under ROC Curve=1.000;
Correct Classification Rate=100%
Rank Sensitivity
Healthy Cells/Cancer Cells 1 14897
Segmented Neutrophils/Cancer Cells
Erythrocytes/Cancer Cells
Thrombocytes/Cancer Cells
2
3
4
13757
12803
12218
Leucocytes/Cancer Cells
Lymphocytes/Cancer Cells
Eosinophils/Cancer Cells
Monocytes/Cancer Cells
Stick Neutrophils/Cancer Cells
5
6
7
8
9
9573
9059
8261
7525
6793

14. Bootstrap Simulation n=701
Significant Factors
(Number of Samples=3333)
Rank Kendall’Tau-A P<
Lymphocytes/Cancer Cells 1 0.269 0.000
Leucocytes/Cancer Cells 2 0.223 0.000
Healthy Cells/Cancer Cells 3 0.211 0.000
Erythrocytes/Cancer Cells 4 0.193 0.000
Thrombocytes/Cancer Cells 5 0.192 0.000
Segmented Neutrophils/Cancer Cells 6 0.173 0.000
Monocytes/Cancer Cells 7 0.111 0.000
PT Early—Invasive Cancer 8 0.107 0.000
PT N0---N12 9 -0.092 0.001
Stick Neutrophils/Cancer Cells 10 0.073 0.01
Eosinophils/Cancer Cells 11 0.067 0.05
Results of Bootstrap Simulation in Prediction of Lung Cancer
Patients Survival after Lobectomies/Pneumonectomies (n=701):

15. Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Lung
Cancer Patients Survival after Lobectomies/Pneumonectomies (n=701):

16. Prognostic Equation Models of Lung Cancer Patients Survival
after Lobectomies/Pneumonectomies (n=701):

17. Prognostic Equation Models of Lung Cancer Patients Survival
after Lobectomies/Pneumonectomies (n=701):

18. Prognostic SEPATH-Model of Lung Cancer Patients Survival
after Lobectomies/Pneumonectomies (n=701):

19. 1. Lung Cancer Patients survival after radical procedures
significantly depended on Cell Ratio Factors.
2. Cell Ratio Factors significantly affect phase transition
early—invasive cancer and lymph node metastases.
Conclusion:

20. 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