Lung Cancer: 10-Year Survival

elcc-congress.org
LUNG CANCER: 10-YEAR SURVIVAL
#358
Kshivets Oleg
Surgery Department, Roshal Hospital, Moscow, Russia
No disclosures
e-mail: okshivets@yahoo.com

EUROPEAN LUNG CANCER VIRTUAL CONGRESS 2021
DECLARATION OF INTERESTS
Oleg Kshivets
No disclosures

LUNG CANCER: 10-YEAR SURVIVAL #358
Oleg Kshivets, MD, PhD
Surgery Department, Roshal Hospital, Roshal, Moscow, Russia
OBJECTIVE: 10-Year survial (10YS) after radical surgery for non-small cell lung cancer (LC) patients (LCP) (T1-4N0-2M0) was analyzed.
METHODS: We analyzed data of 768 consecutive LCP (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; early LC=214, invasive LC=554; right
LC=412, left LC=356; central=290; peripheral=478. Variables selected for 10YS 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 yers – 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).
AT significantly improved 10YS (52.4% vs. 27.7%) (P=0.00002 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 10YS 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, color index (P=0.000-0.039).
Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 10YS and PT early-invasive LC (rank=1),
thrombocytes/CC (rank=2), PT N0—N12(rank=3), segmented neutrophils/CC (4), healthy cells/CC (5), lymphocytes/CC (6), erythrocytes/CC (7), stick
neutrophils/CC (8), eosinophils/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: 10-Year survival 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) anthropometric data; 10) surgery type; 11) tumor localization.
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.

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

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

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%

GENERAL LUNG CANCER PATIENTS SURVIVAL AFTER COMPLETE
LOBECTOMIES/PNEUMONECTOMIES (KAPLAN-MEIER) (N=768):
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

RESULTS OF UNIVARIATE ANALYSIS OF PHASE TRANSITION EARLY—INVASIVE
CANCER IN PREDICTION OF LUNG CANCER PATIENTS SURVIVAL (N=768):
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
-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 N0—N1-2 IN
PREDICTION OF LUNG CANCER PATIENTS SURVIVAL (N=768):
10-Year Survival of Lung Cancer Patients with N0=78.3%;
10-Year Survival of Lung Cancer Patients with N1-2=35.2%;
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 ADJUVANT CHEMOIMMUNORADIOTHERAPY IN
PREDICTION OF LUNG CANCER PATIENTS SURVIVAL WITH N1-2 (N=252):
10-Year Survival of LCP after AT=52.4%;
10-Year Survival of LCP after Surgery=27.7%;
Complete Censored
0 5 10 15 20 25 30
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, n=164
Adjuvant Chemoimmunoradiotherapy, n=88

10-Year Survival after Lobectomies=72%;
10-Year Survival after Pneumonectomies=46.9%;
Complete Censored
0 5 10 15 20 25 30 35
-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
Pneumonectomies, n=254
Lobectomies, n=514
RESULTS OF UNIVARIATE ANALYSIS OF TYPE OF PROCEDURES IN
PREDICTION OF LUNG CANCER PATIENTS SURVIVAL (N=768):

RESULTS OF UNIVARIATE ANALYSIS OF GENDER IN PREDICTION
OF LUNG CANCER PATIENTS SURVIVAL (N=768):
10-Year Survival of Female LCP=73.4%;
10-Year Survival of Male LCP=63.4%;
Complete Censored
0 5 10 15 20 25 30 35
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
male, n=660
female, n=108

RESULTS OF COX REGRESSION MODELING IN PREDICTION OF LUNG CANCER
PATIENTS SURVIVAL AFTER COMPLETE LOBECTOMIES/PNEUMONECTOMIES (N=768):
Cox Proportional Hazards Results,
LCP T1-4N0-2M0, n=768
Parameter
Estimate
Standard
Error
Chi-square P value
Thrombocytes/Cancer Cells -0.00550 0.001579 12.14276 0.000493
Healthy Cells/Cancer Cells 0.07391 0.024958 8.77037 0.003062
Adjuvant Chemoimmunoradiotherapy -1.13036 0.201727 31.39806 0.000000
Phase Transition N0---N12 1.12121 0.144416 60.27584 0.000000
Phase Transition Early-Invasive Cancer -1.47130 0.341717 18.53830 0.000017
Histology 0.35066 0.084684 17.14621 0.000035
G1-3 0.36443 0.087580 17.31503 0.000032
Color Index -2.18363 0.917025 5.67018 0.017256
Glucose -0.32526 0.078234 17.28559 0.000032
Prothrombin Index 0.03372 0.006854 24.20847 0.000001
Bilirubin 0.05124 0.018274 7.86319 0.005045
Recalcification Time -0.00444 0.001711 6.73236 0.009468
Heparin Tolerance 0.00392 0.000662 35.06287 0.000000
Thrombocytes (tot) 0.00172 0.000341 25.43339 0.000000
Monocytes -0.05039 0.024421 4.25828 0.039059
Weight -0.03451 0.008725 15.64460 0.000076

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
Phase Transition Early--Invasive Cancer 1 11646
Thrombocytes/Cancer Cells 2 7184
Phase Transition N0--N12
Segmented Neutrophils/Cancer Cells
Healthy Cells/Cancer Cells
Lymphocytes/Cancer Cells
Erythrocytes/Cancer Cells
Stick Neutrophils/Cancer Cells
Eosinophils/Cancer Cells
Leucocytes/Cancer Cells
Monocytes/Cancer Cells
3
4
5
6
7
8
9
10
11
6656
4154
4407
3993
3370
2963
2224
1566
1206

RESULTS OF BOOTSTRAP SIMULATION IN PREDICTION OF LUNG CANCER PATIENTS
SURVIVAL AFTER LOBECTOMIES/PNEUMONECTOMIES (N=701):
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
Lymphocytes (tot) 6 0.183 0.000
Segmented Neutrophils/Cancer Cells 7 0.173 0.000
Tumor Size 8 -0.118 0.000
Monocytes/Cancer Cells 9 0.111 0.000
PT Early---Invasive Cancer 10 0.107 0.000
Lymphocytes (%) 11 0.105 0.000
Segmented Neutrophils (%) 12 -0.102 0.000
Lymphocytes (abs) 13 0.096 0.000
Prothrombin Index 14 -0.094 0.001
T1-4 15 -0.094 0.001
PT N0---N12 16 -0.092 0.001
Procedures Type 17 0.087 0.01
Histology 18 0.076 0.01
Stick Neutrophils/Cancer Cells 19 0.073 0.01
Eosinophils/Cancer Cells 20 0.067 0.05
Age 21 -0.067 0.05
Fibrinogen 22 -0.052 0.05

RESULTS OF KOHONEN SELF-ORGANIZING NEURAL NETWORKS COMPUTING IN PREDICTION OF
LUNG CANCER PATIENTS SURVIVAL AFTER LOBECTOMIES/PNEUMONECTOMIES (N=701):

LUNG CANCER DYNAMICS:

PROGNOSTIC EQUATION MODELS OF LUNG CANCER PATIENTS SURVIVAL
AFTER LOBECTOMIES/PNEUMONECTOMIES (N=701):

PROGNOSTIC SEPATH-MODEL OF LUNG CANCER PATIENTS SURVIVAL
AFTER LOBECTOMIES/PNEUMONECTOMIES (N=701):

Conclusion:
10-Year survival 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 chemoimmunoradiotherapy;
8) lung cancer characteristics;
9) anthropometric data;
10) surgery type;
11) tumor localization.

Conclusion:
Optimal diagnosis and treatment strategies for lung cancer are:
1) screening and early detection;
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.

elcc-congress.org
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

Lung Cancer: 10-Year Survival

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