Survival Outcomes in Patients with Lung Cancer after Radical Surgery

1. Survival Outcomes in
Patients with Lung Cancer
after Radical Surgery
Kshivets Oleg, MD, PhD
Surgery Department, Roshal Hospital,
Roshal, Moscow, Russia

2. Survival Outcomes in Patients with
Lung Cancer after Radical Surgery
Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia
OBJECTIVE: Survival outcomes of radical surgery in non-small cell lung cancer (LC) pa­tients (LCP) (T1-
4N0-2M0) were analyzed.
METHODS: We analyzed data of 757 consecutive LCP (age=57.6±8.2 years; tumor size=4.1±2.4 cm)
radically operated (R0) and monitored in 1985-2018 (m=654, f=103; upper lobectomies=272, lower
lobectomies=176, middle lobectomies=18, bilobectomies=42, pneumonectomies=249, mediastinal lymph
node dissection=757; combined procedureswith resection of trachea, carina, atrium, aorta, VCS, vena
azygos, pericardium, liver, diaphragm, ribs, esophagus=192; only surgery-S=612, adjuvant
chemoimmunoradiotherapy-AT=145: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy45-50Gy;
T1=317, T2=251, T3=132, T4=57; N0=509, N1=130, N2=118, M0=757; G1=194, G2=238, G3=325;
squamous=415, adenocarcinoma=292, large cell=50; early LC=212, invasive LC=545. 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 2245.6±1750.5 days and cumulative 5-year survival (5YS) reached
73.1%, 10 years – 64.4%, 20 years – 42.8%. 496 LCP lived more than 5 years (LS=3124.2±1539.1 days), 142
LCP – more than 10 years (LS=5078±978.5 days).195 LCP died because of LC (LS=560±372.1 days). AT
significantly improved 5YS (64.4% vs. 34.1%) (P=0.00002 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, weight (P=0.000-0.030). Neural networks, genetic algorithm selection and bootstrap
simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12(rank=2),
erythrocytes/CC (3), thrombocytes/CC (4), healthy cells/CC (5), eosinophils/CC (6), segmented
neutrophils/CC (7), stick neutrophils/CC (8), lymphocytes/CC (9), leucocytes/CC (10), monocytes/CC (11).
Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: Survival outcomes in LCP after radical proceduressignificantly 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) anthropometric data. Optimal diagnosis and treatment
strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic
surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph
node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP
with unfavorable prognosis.

3. Data:
• Males…………………………………….….654
• Females……............................................103
• Age=57.6±8.2 years
• Tumor Size=4.1±2.4 cm
• Only Surgery.…......................................612
• Adjuvant Chemoimmunoradiotherapy
• (CAV/gemzar+cisplatin+thymalin/taktivin,
• 5-6 cycles+ Radiotherapy 45-50Gy).....145

4. Radical Procedures:
• Upper Lobectomies …………………….…272
• Lower Lobectomies ……………...............176
• Middle Lobectomies………………….…..…18
• Bilobectomies…………………………….…..42
• Pneumonectomies………………………....249
• Combined Procedures with Resection of
Carina, Trachea, Atrium, Aorta, Liver, Vena
Cava Superior, Vena Azygos, Diaphragm,
Pericardium, Ribs, Esophagus (R0)…….192
• Mediastinal Lymph Node Dissection.……757

5. Staging:
• T1……..317 N0..……509 G1…..…194
T2……..251 N1…......130 G2……..238
• T3……..132 N2..……118 G3….…325
• T4……….57 M0……...757 M1….…...0
• Adenocarcinoma………………………...292
• Squamous Cell Carcinoma……......…..415
• Large Cell Carcinoma………...................50
• Early Cancer…………...………………....212
• Invasive Cancer…………..……………...545

6. Survival Rate:
• Alive……………..................................507 (67%)
• 5-Year Survivors…………..................496 (65.5%)
• 10-Year Survivors…………................142 (18.8%)
• Losses…………………………………..195 (25.8%)
• General Life Span=2245.6±1750.5 days
• For 5-Year Survivors=3124.2±1539.1 days
• For 10-Year Survivors=5078±978.5 days
• For Losses=560±372.1 days
• Cumulative 5-Year Survival……..………....73.1%
• Cumulative 10-Year Survival……..…...…...64.4%
• Cumulative 20-Year Survival……………....42.8%

7. General Lung Cancer Patients Survival after Complete
Lobectomies/Pneumonectomies (Kaplan-Meier) (n=757):
Survival Function
General Lung Cancer Patients Survival, n=757
5-Year Survival=73.1%; 10-Year Survival=64.4%; 20-Year Survival=42.8%
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
CumulativeProportionSurviving

8. Results of Univariate Analysis of Phase Transition Early—Invasive
Cancer in Prediction of Lung Cancer Patients Survival (n=757):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of Early Lung Cancer Patients=100%;
5-Year Survival of Invasive Lung Cancer Patients=62.3%;
P=0.00000 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
1.0CumulativeProportionSurviving
Invasive Lung Cancer, n=545
Early Lung Cancer, n=212

9. Results of Univariate Analysis of Phase Transition N0—N1-2
in Prediction of Lung Cancer Patients Survival (n=757):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of LCP with N0=86.9%;
5-Year Survival of LCP with N1-2=43.5%;
P=0.00000 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
CumulativeProportionSurviving
LCP with N1-2, n=248
LCP with N0, n=509

10. Results of Univariate Analysis of Adjuvant
ChemoimmunoradioTherapy in Prediction of Lung Cancer
Patients Survival with N1-2 (n=248):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of LCP with N1-2 after Adjuvant Chemoimmunoradiotherapy=64.4%;
5-Year Survival of LCP with N1-2 after Surgery alone=31.4%;
P=0.00002 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30
Years after Lobectomies/Pneumonectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Only Surgery, n=164
Adjuvant Chemoimmunoradiotherapy, n=84

11. Results of Univariate Analysis of Type of Procedures in
Prediction of Lung Cancer Patients Survival (n=575):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of LCP after Lobectomies=77.6%;
5-Year Survival after Pneumonectomies=63.2%;
P=0.00003 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35
Years after Lobectomies/Pneumonectomies
-0.1
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Pneumonectomies, n=249
Lobectomies/Bilobectomies, n=508

12. Results of Cox Regression Modeling in Prediction of Lung
Cancer Patients Survival after Complete
Lobectomies/Pneumonectomies (n=575):
Factors
Parameter Estimates: LCP=757; Cox Proportional Hazards Results
Parameter
Estimate
Standard
Error
Chi-square P value
95%
Lower
CL
95%
Upper
CL
Hazard
Ratio
95%
Hazard
Ratio
Lower CL
95%
Hazard
Ratio
Upper
CL
Glucose -0.29611 0.079655 13.81892 0.000201 -0.45223 -0.13999 0.743707 0.636208 0.869369
Prothrombin Index 0.03009 0.006908 18.97603 0.000013 0.01655 0.04363 1.030551 1.016691 1.044599
Recalcification Time -0.00475 0.001715 7.68729 0.005561 -0.00812 -0.00139 0.995257 0.991918 0.998608
Heparin Tolerance 0.00384 0.000678 32.08220 0.000000 0.00251 0.00517 1.003846 1.002514 1.005180
Phase Transition Early—Invasive Cancer -1.40608 0.342982 16.80648 0.000041 -2.07831 -0.73385 0.245102 0.125141 0.480059
THR/Cancer Cells -0.00596 0.001746 11.65343 0.000641 -0.00938 -0.00254 0.994058 0.990662 0.997465
Healthy Cells/Cancer Cells 0.08035 0.027222 8.71164 0.003162 0.02699 0.13370 1.083663 1.027360 1.143050
Thrombocytes tot 0.00172 0.000381 20.49500 0.000006 0.00098 0.00247 1.001726 1.000978 1.002474
Eosinophils tot -0.25604 0.102288 6.26573 0.012310 -0.45652 -0.05556 0.774110 0.633484 0.945955
Monocytes tot 0.89550 0.422471 4.49299 0.034034 0.06747 1.72353 2.448554 1.069799 5.604250
Phase Transition N0--N12 1.09366 0.151263 52.27557 0.000000 0.79719 1.39013 2.985172 2.219291 4.015360
Adjuvant Chemoimmunoradiotherapy -1.44527 0.238150 36.82943 0.000000 -1.91203 -0.97850 0.235683 0.147780 0.375874
Type of Procedures -0.45023 0.169289 7.07299 0.007825 -0.78203 -0.11843 0.637484 0.457478 0.888318
Weight -0.05362 0.011898 20.31158 0.000007 -0.07694 -0.03030 0.947792 0.925946 0.970153
Histology 0.35730 0.086388 17.10604 0.000035 0.18798 0.52661 1.429458 1.206808 1.693188
G1-3 0.35795 0.087042 16.91187 0.000039 0.18735 0.52855 1.430398 1.206053 1.696474
Lymphocytes -0.01521 0.007154 4.52155 0.033470 -0.02923 -0.00119 0.984904 0.971191 0.998810
Monocytes abs -5.16252 2.089104 6.10666 0.013467 -9.25709 -1.06795 0.005727 0.000095 0.343711

13. Results of Discriminant Function Analysis in Prediction of
Lung Cancer Patients Survival after Complete
Lobectomies/Pneumonectomies (n=691):
N=691
Discriminant Function Analysis Summary Wilks' Lambda:
.59004 approx. F (18,672)=25.939 p<0.0000
Wilks'
Lambda
Partial
Lambda
F-remove
(1,672)
p-value Toler.
1-Toler.
(R-Sqr.)
Rh-factor 0.594051 0.993253 4.56483 0.032995 0.962767 0.037233
Tumor Grouth 0.593833 0.993618 4.31609 0.038133 0.869521 0.130479
Histology 0.594005 0.993329 4.51276 0.034007 0.805384 0.194616
G1-3 0.596197 0.989677 7.00919 0.008299 0.912483 0.087517
Segmented Neutrophils 0.614438 0.960297 27.78320 0.000000 0.168645 0.831356
Glucose 0.596510 0.989158 7.36567 0.006819 0.946959 0.053041
Prothrombin Index 0.611490 0.964927 24.42561 0.000001 0.964110 0.035890
Recalcification Time 0.599547 0.984148 10.82436 0.001054 0.812726 0.187274
Fibrinogen-B 0.597831 0.986973 8.86947 0.003004 0.965301 0.034699
Heparin Tolerance 0.613011 0.962533 26.15779 0.000000 0.775584 0.224416
Phase Transition Early Lung Cancer---Invasive Lung Cancer 0.631723 0.934022 47.46910 0.000000 0.632469 0.367531
Stick Neutrophils/Cancer Cells 0.595758 0.990407 6.50907 0.010953 0.394660 0.605340
Lymphocytes/Cancer Cells 0.597045 0.988273 7.97409 0.004886 0.391581 0.608419
Thrombocytes tot 0.598061 0.986593 9.13207 0.002607 0.595617 0.404383
Leucocytes tot 0.617672 0.955269 31.46675 0.000000 0.107192 0.892808
Stick Neutrophils tot 0.601915 0.980277 13.52058 0.000255 0.323594 0.676406
Phase Transition N0---N12 0.662005 0.891297 81.95739 0.000000 0.807784 0.192216
Adjuvant Chemoimmunoradiotherapy 0.596318 0.989478 7.14633 0.007694 0.717937 0.282063

14. Results of Neural Networks Computing in Prediction of Lung Cancer
Patients Survival after Complete Lobectomies/Pneumonectomies (n=691):
Neural Networks: n=691;
Baseline Error=0.000;
Area under ROC Curve=1.000;
Correct Classification Rate=100%
Rank Sensitivity
Phase Transition Early--Invasive Cancer 1 25177
Phase Transition N0--N12 2 18552
Erythrocytes/Cancer Cells
Thrombocytes/Cancer Cells
Healthy Cells/Cancer Cells
Eosinophils/Cancer Cells
Segmented Neutrophils/Cancer Cells
Stick Neutrophils/Cancer Cells
3
4
5
6
7
8
16080
14885
14709
13520
10040
8423
Lymphocytes/Cancer Cells 9 7687
Leucocytes/Cancer Cells
Monocytes/Cancer Cells
10
11
6774
5997

15. Results of Bootstrap Simulation in Prediction of Lung Cancer
Patients Survival after Lobectomies/Pneumonectomies (n=691):
Bootstrap Simulation
Significant Factors (Number of Samples=3333)
Rank Kendall’Tau-A P<
Healthy Cells/Cancer Cells 1 -0.229 0.000
Erythrocytes/Cancer Cells 2 -0.225 0.000
Lymphocytes/Cancer Cells 3 -0.220 0.000
Thrombocytes/Cancer Cells 4 -0.202 0.000
Phase Transition N0---N12 5 0.200 0.000
Leucocytes/Cancer Cells 6 -0.189 0.000
Tumor Size 7 0.158 0.000
Prothrombin Index 8 0.154 0.000
Eosinophils/Cancer Cells 9 -0.148 0.000
Phase Transition Early---Invasive Cancer 10 -0.146 0.000
Monocytes/Cancer Cells 11 -0.140 0.000
Segmented Neutrophils/Cancer Cells 12 -0.138 0.000
T1-4 13 0.137 0.000
Weight 14 -0.098 0.000
Segmented Neutrophils (%) 15 0.098 0.001
Erythrocytes (tot) 16 -0.092 0.000
G1-3 17 0.085 0.001
ESS 18 0.085 0.001
Lymphocytes (tot) 19 -0.082 0.01
Lymphocytes (%) 20 -0.078 0.01
Only Surgery 21 -0.073 0.01
Glucose 22 -0.072 0.01
Heparin Tolerance 23 0.067 0.05
Eosinophils (%) 24 -0.057 0.05
Procedures Type 25 -0.055 0.05

16. Results of Kohonen Self-Organizing Neural Networks
Computing in Prediction of Lung Cancer Patients Survival
after Lobectomies/Pneumonectomies (n=691):

17. Lung Cancer Dynamics:

18. Prognostic Equation Models of Lung Cancer Patients
Survival after Lobectomies/Pneumonectomies (n=691):

19. Prognostic SEPATH-Model of Lung Cancer Patients Survival
after Lobectomies/Pneumonectomies (n=691):

20. 5-YEAR SURVIVAL OF LUNG CANCER PATIENTS
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 CHEMOIMMUNORADIOTHERAPY;
8) CANCER CHARACTERISTICS ;
9) SURGERY TYPE;
10) ANTHROPOMETRIC DATA.
Conclusion:

21. OPTIMAL DIAGNOSIS AND TREATMENT
STRATEGIES FOR LUNG CANCER ARE:
1) SCREENING AND EARLY DETECTION OF
LUNG CANCER;
2) AVAILABILITY OF EXPERIENCED THORACIC
SURGEONS BECAUSE OF COMPLEXITY OF
RADICAL PROCEDURES;
3) AGGRESSIVE EN BLOCK SURGERY AND
ADEQUATE LYMPH NODE DISSECTION FOR
COMPLETENESS;
4) PRECISE PREDICTION;
5) ADJUVANT CHEMOIMMUNORADIOTHERAPY
FOR LUNG CANCER PATIENTS WITH
UNFAVORABLE PROGNOSIS.
Conclusion:

22. 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