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Oleg Kshivets, MD, PhD
Surgery Department, Roshal Hospital
Roshal, Moscow, Russia
Combined Lobectomies and Pneumonectomies:
Survival Outcomes in Patients with Local Advanced
Lung Cancer
Abstract
Combined Lobectomies and Pneumonectomies: Survival Outcomes in Patients with Local Advanced Lung Cancer
Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia
OBJECTIVE: The survival of patients with local advanced of lung cancer (LC) takes several months. Radical operations are
extremely complex and remain the prerogative of several best thoracic surgeons of the world. The search of optimal treatment plan
for LC patients (LCP) with stage T3-4N0-2M0 was realized. We examined factors in terms of precise prediction of 5-year survival
(5YS) of local advanced LCP after complete (R0) combined lobectomies/pneumonectomies (LP).
METHODS: We analyzed data of 192 consecutive LCP (age=58.1±8.3 years; tumor size=6.8±2.6 cm) radically operated and
monitored in 1985-2019 (m=167, f=25; bi/lobectomies=82, pneumonectomies=110, mediastinal lymph node dissections=192;
combined LP with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs,
esophagus=192; only surgery-S=116, adjuvant chemoimmunoradiotherapy-AT=76: CAV/gemzar + cisplatin + thymalin/taktivin +
radiotherapy 45-50Gy; T3=133, T4=59; N0=93, N1=42, N2=57, M0=192; G1=40, G2=50, G3=102; squamous=115,
adenocarcinoma=62, large cell=15, central=110, peripheral=82. 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 1632.2±1729.4 days and cumulative 5YS reached 61.1%, 10 years – 49%, 20 years –
43.2%. 88 LCP lived more than 5 years without cancer (LS=2960.3±1773.2 days), 20 – more than 10 years (LS=5744.9±1842.9
days). 68 LCP died because of LC (LS=466.5±344.4 days). AT significantly improved 5YS (72.3% vs. 54.6%) (P=0.048 by log-rank
test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, cell ratio factors (ratio between cancer cells-CC
and blood cells subpopulations), AT (P=0.005-0.049). Neural networks, genetic algorithm selection and bootstrap simulation
revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), eosinophils/CC (3), healthy cells/CC (4), stick
neutrophils/CC (5), lymphocytes/CC (6), segmented neutrophils/CC (7), erythrocytes/CC (8), monocytes/CC (9), leucocytes/CC
(10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
CONCLUSIONS: 5YS of local advanced non-small cell LCP after combined radical procedures significantly depended on: tumor
characteristics, blood cell circuit, cell ratio factors, biochemical factors, hemostasis system, anthropometric data and adjuvant
treatment. Optimal strategies for local advanced LCP are: 1) availability of very experienced thoracic surgeons because of
complexity radical procedures; 2) aggressive en block surgery and adequate lymph node dissection for completeness; 3) precise
prediction; 4) AT for LCP with unfavorable prognosis.
Data:
Males…………………………………….….167
Females……..............................................25
Age=58.1±8.3 years
Tumor Size=6.8±2.6 cm
Only Surgery.….......................................116
Adjuvant Chemoimmunoradiotherapy
(CAV/gemzar+cisplatin+thymalin/taktivin,
5-6 cycles+ Radiotherapy 45-50Gy).........76
Radical Procedures:
Bi/Lobectomies …………………………..…….…..82
Pneumonectomies……………………………......110
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.……..…..192
Staging:
T3……..133 N0..…….93 G1…..….40
T4………59 N1….......42 G2………50
N2..…….57 G3….…102
M0…….192 M1….…….0
Adenocarcinoma………………………….62
Squamous Cell Carcinoma……......…..115
Large Cell Carcinoma………...................15
Central Lung Cancer………………...….110
Peripheral Lung Cancer………………….82
General Lung Cancer Patients Survival after Combined
Lobectomies/Pneumonectomies (Kaplan-Meier) (n=192):
Survival Function
General Lung Patients Survival, n=192
5-Year Survival=61.1%; 10-Year Survival=49%; 20-Year Survival=43.2%
Complete Censored
-5 0 5 10 15 20 25 30
Years after Combined Lobectomies/Pneumonectomies
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Survival Rate:
Alive……………..................................114 (59.4%)
5-Year Survivors…………....................88 (45.8%)
10-Year Survivors……………..............20 (10.4%)
Losses……………………………………68 (35.4%)
General Life Span=1632.2±1729.4 days
For 5-Year Survivors=2960.3±1773.2 days
For 10-Year Survivors=5744.9±1842.9 days
For Losses=466.5±344.4 days
Cumulative 5-Year Survival……..………....61.1%
Cumulative 10-Year Survival…….....….........49%
Cumulative 20-Year Survival……………....43.2%
Results of Univariate Analysis of Phase Transition N0—N1-2 in
Prediction of Lung Cancer Patients Survival (n=192):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival for LCP with N0=73.6%; 5-Year Survival for LCP with N1-2=49%;
P=0.00038 by Log-Rank Test
Complete Censored
0 5 10 15 20 25
Years after Combined Lobectomies/Pneumonectomies
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
LCP with N1-2, n=99
LCP with N0, n=93
Results of Univariate Analysis of Adjuvant
ChemoimmunoradioTherapy in Prediction of Lung Cancer
Patients Survival (n=192):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of LCP after AT=72.3%; 5-Year Survival of LCP after Surgery Alone=54.6%;
P=0.00371 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35
Years after Combined Lobectomies/Pneumonectomies
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Only Surgery, n=116
Adjuvant Chemoimmunoradiotherapy, n=76
Results of Cox Regression Modeling in Prediction of Lung
Cancer Patients Survival after Combined
Lobectomies/Pneumonectomies (n=192):
Factors
Parameter
Estimate
Standard
Error
Chi-
square
P value
95%
Lower CL
95%
Upper CL
Leucocytes/Cancer Cells -0.431498 0.173263 6.202197 0.012759 -0.77109 -0.091909
Stick Neutrophils/ Cancer Cells 1.170955 0.550455 4.525184 0.033399 0.09208 2.249828
Segmented Neutrophils/Cancer Cells 0.449070 0.228264 3.870365 0.049146 0.00168 0.896460
Phase Transition N0---N12 0.613495 0.240454 6.509657 0.010729 0.14221 1.084777
Adjuvant Chemoimmunoradiotherapy -0.750702 0.264714 8.042338 0.004570 -1.26953 -0.231873
Results of Discriminant Function Analysis in Prediction of
Lung Cancer Patients Survival after Combined
Lobectomies/Pneumonectomies (n=192):
N=192
Discriminant Function Analysis
Wilks' Lambda: .74573 approx. F (6,185)=10.513 p< .0000
Wilks'
Lambda
Partial
Lambda
F-remove
(1,185)
p-value Toler.
1-Toler.
(R-Sqr.)
Age 0.781180 0.954618 8.79471 0.003419 0.994734 0.00526
T3-4 0.788499 0.945757 10.61051 0.001338 0.986138 0.01386
Prothrombin Index 0.792095 0.941464 11.50249 0.000850 0.980494 0.01950
Fibrinogen-B 0.765641 0.973993 4.93984 0.027456 0.998629 0.00137
Stick Neutrophils/Cancer Cells 0.765966 0.973580 5.02042 0.026240 0.988483 0.01151
Phase Transition N0---N12 0.771925 0.966064 6.49870 0.011607 0.969024 0.03097
Results of Neural Networks Computing in Prediction of Lung
Cancer Patients Survival after Combined
Lobectomies/Pneumonectomies (n=156):
Neural Networks: Baseline
Error=0.000; Area under ROC
Curve=1.000; Correct
Classification Rate=100%; n=192
Rank Sensitivity
Phase Transition N0---N12 1 1199
Thrombocytes/Cancer Cells
Eosinophils/Cancer Cells
Healthy Cells/Cancer Cells
Stick Neutrophils/Cancer Cells
Lymphocytes/Cancer Cells
Segmented Neutrophils/Cancer Cells
2
3
4
5
6
7
637
474
437
376
372
333
Erythrocytes/Cancer Cells 8 299
Monocytes/Cancer Cells
Leucocytes/Cancer Cells
9
10
261
159
Results of Bootstrap Simulation in Prediction of Lung
Cancer Patients Survival after Combined
Lobectomies/Pneumonectomies (n=156):
Significant Factors
(Number of Samples=3333)
Rank Kendal Tau-A P<
Prothrombin Index 1 -0.209 0.001
Phase Transition N0---N12 2 -0.176 0.01
Glucose 3 0.133 0.05
Weight 4 0.125 0.05
Erythrocytes/Cancer Cells 5 0.124 0.05
Age 6 -0.118 0.05
Heparin Tolerance 7 -0.118 0.05
Healthy Cells/Cancer Cells 8 0.117 0.05
Monocytes/Cancer Cells 9 0.117 0.05
Eosinophils/Cancer Cells 10 0.115 0.05
ESS 11 -0.112 0.05
Erythrocytes tot. 12 0.112 0.05
Results of Kohonen Self-Organizing Neural Networks
Computing in Prediction of Lung Cancer Patients Survival
after Combined Lobectomies/Pneumonectomies (n=156):
Lung Cancer Dynamics:
Prognostic Equation Models of Lung Cancer Patients Survival
after Combined Lobectomies/Pneumonectomies (n=156):
Prognostic SEPATH-Model of Lung Cancer Patients Survival
after Combined Lobectomies/Pneumonectomies (n=156):
Conclusion:
5-Year Survival of Local Advanced Non-
Small Cell Lung Cancer Patients after
Combined Radical Lobectomies and
Pneumonectomies Significantly
Depended on:
1) Phase Transition N0--N12;
2) Cell Ratio Factors;
3) Blood Cell Circuit;
4) Biochemical Factors;
5) Adjuvant Chemoimmunoradiotherapy;
6) Cancer Characteristics ;
7) Anthropometric Data.
Conclusion:
Optimal Strategies for Local Advanced
Non-Small Cell Lung Cancer Patients are:
1) Availability of Very Experienced
Thoracic Surgeons because of
Complexity Radical Procedures;
2) Aggressive En Block Surgery and
Adequate Lymph Node Dissection for
Completeness;
3) Precise Prediction;
4) Adjuvant Chemoimmunoradiotherapy
for Lung Cancer Patients with
Unfavorable Prognosis.
Address:
Oleg Kshivets, M.D., Ph.D.
Consultant Thoracic, Abdominal,
General Surgeon & Surgical Oncologist

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Kshivets Hong Kong Sydney2020

  • 1. Oleg Kshivets, MD, PhD Surgery Department, Roshal Hospital Roshal, Moscow, Russia Combined Lobectomies and Pneumonectomies: Survival Outcomes in Patients with Local Advanced Lung Cancer
  • 2. Abstract Combined Lobectomies and Pneumonectomies: Survival Outcomes in Patients with Local Advanced Lung Cancer Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia OBJECTIVE: The survival of patients with local advanced of lung cancer (LC) takes several months. Radical operations are extremely complex and remain the prerogative of several best thoracic surgeons of the world. The search of optimal treatment plan for LC patients (LCP) with stage T3-4N0-2M0 was realized. We examined factors in terms of precise prediction of 5-year survival (5YS) of local advanced LCP after complete (R0) combined lobectomies/pneumonectomies (LP). METHODS: We analyzed data of 192 consecutive LCP (age=58.1±8.3 years; tumor size=6.8±2.6 cm) radically operated and monitored in 1985-2019 (m=167, f=25; bi/lobectomies=82, pneumonectomies=110, mediastinal lymph node dissections=192; combined LP with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=192; only surgery-S=116, adjuvant chemoimmunoradiotherapy-AT=76: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T3=133, T4=59; N0=93, N1=42, N2=57, M0=192; G1=40, G2=50, G3=102; squamous=115, adenocarcinoma=62, large cell=15, central=110, peripheral=82. 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 1632.2±1729.4 days and cumulative 5YS reached 61.1%, 10 years – 49%, 20 years – 43.2%. 88 LCP lived more than 5 years without cancer (LS=2960.3±1773.2 days), 20 – more than 10 years (LS=5744.9±1842.9 days). 68 LCP died because of LC (LS=466.5±344.4 days). AT significantly improved 5YS (72.3% vs. 54.6%) (P=0.048 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), AT (P=0.005-0.049). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), eosinophils/CC (3), healthy cells/CC (4), stick neutrophils/CC (5), lymphocytes/CC (6), segmented neutrophils/CC (7), erythrocytes/CC (8), monocytes/CC (9), leucocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0). CONCLUSIONS: 5YS of local advanced non-small cell LCP after combined radical procedures significantly depended on: tumor characteristics, blood cell circuit, cell ratio factors, biochemical factors, hemostasis system, anthropometric data and adjuvant treatment. Optimal strategies for local advanced LCP are: 1) availability of very experienced thoracic surgeons because of complexity radical procedures; 2) aggressive en block surgery and adequate lymph node dissection for completeness; 3) precise prediction; 4) AT for LCP with unfavorable prognosis.
  • 3. Data: Males…………………………………….….167 Females……..............................................25 Age=58.1±8.3 years Tumor Size=6.8±2.6 cm Only Surgery.….......................................116 Adjuvant Chemoimmunoradiotherapy (CAV/gemzar+cisplatin+thymalin/taktivin, 5-6 cycles+ Radiotherapy 45-50Gy).........76
  • 4. Radical Procedures: Bi/Lobectomies …………………………..…….…..82 Pneumonectomies……………………………......110 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.……..…..192
  • 5. Staging: T3……..133 N0..…….93 G1…..….40 T4………59 N1….......42 G2………50 N2..…….57 G3….…102 M0…….192 M1….…….0 Adenocarcinoma………………………….62 Squamous Cell Carcinoma……......…..115 Large Cell Carcinoma………...................15 Central Lung Cancer………………...….110 Peripheral Lung Cancer………………….82
  • 6. General Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (Kaplan-Meier) (n=192): Survival Function General Lung Patients Survival, n=192 5-Year Survival=61.1%; 10-Year Survival=49%; 20-Year Survival=43.2% Complete Censored -5 0 5 10 15 20 25 30 Years after Combined Lobectomies/Pneumonectomies 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 CumulativeProportionSurviving
  • 7. Survival Rate: Alive……………..................................114 (59.4%) 5-Year Survivors…………....................88 (45.8%) 10-Year Survivors……………..............20 (10.4%) Losses……………………………………68 (35.4%) General Life Span=1632.2±1729.4 days For 5-Year Survivors=2960.3±1773.2 days For 10-Year Survivors=5744.9±1842.9 days For Losses=466.5±344.4 days Cumulative 5-Year Survival……..………....61.1% Cumulative 10-Year Survival…….....….........49% Cumulative 20-Year Survival……………....43.2%
  • 8. Results of Univariate Analysis of Phase Transition N0—N1-2 in Prediction of Lung Cancer Patients Survival (n=192): Cumulative Proportion Surviving (Kaplan-Meier) 5-Year Survival for LCP with N0=73.6%; 5-Year Survival for LCP with N1-2=49%; P=0.00038 by Log-Rank Test Complete Censored 0 5 10 15 20 25 Years after Combined Lobectomies/Pneumonectomies 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 CumulativeProportionSurviving LCP with N1-2, n=99 LCP with N0, n=93
  • 9. Results of Univariate Analysis of Adjuvant ChemoimmunoradioTherapy in Prediction of Lung Cancer Patients Survival (n=192): Cumulative Proportion Surviving (Kaplan-Meier) 5-Year Survival of LCP after AT=72.3%; 5-Year Survival of LCP after Surgery Alone=54.6%; P=0.00371 by Log-Rank Test Complete Censored 0 5 10 15 20 25 30 35 Years after Combined Lobectomies/Pneumonectomies 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 CumulativeProportionSurviving Only Surgery, n=116 Adjuvant Chemoimmunoradiotherapy, n=76
  • 10. Results of Cox Regression Modeling in Prediction of Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (n=192): Factors Parameter Estimate Standard Error Chi- square P value 95% Lower CL 95% Upper CL Leucocytes/Cancer Cells -0.431498 0.173263 6.202197 0.012759 -0.77109 -0.091909 Stick Neutrophils/ Cancer Cells 1.170955 0.550455 4.525184 0.033399 0.09208 2.249828 Segmented Neutrophils/Cancer Cells 0.449070 0.228264 3.870365 0.049146 0.00168 0.896460 Phase Transition N0---N12 0.613495 0.240454 6.509657 0.010729 0.14221 1.084777 Adjuvant Chemoimmunoradiotherapy -0.750702 0.264714 8.042338 0.004570 -1.26953 -0.231873
  • 11. Results of Discriminant Function Analysis in Prediction of Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (n=192): N=192 Discriminant Function Analysis Wilks' Lambda: .74573 approx. F (6,185)=10.513 p< .0000 Wilks' Lambda Partial Lambda F-remove (1,185) p-value Toler. 1-Toler. (R-Sqr.) Age 0.781180 0.954618 8.79471 0.003419 0.994734 0.00526 T3-4 0.788499 0.945757 10.61051 0.001338 0.986138 0.01386 Prothrombin Index 0.792095 0.941464 11.50249 0.000850 0.980494 0.01950 Fibrinogen-B 0.765641 0.973993 4.93984 0.027456 0.998629 0.00137 Stick Neutrophils/Cancer Cells 0.765966 0.973580 5.02042 0.026240 0.988483 0.01151 Phase Transition N0---N12 0.771925 0.966064 6.49870 0.011607 0.969024 0.03097
  • 12. Results of Neural Networks Computing in Prediction of Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (n=156): Neural Networks: Baseline Error=0.000; Area under ROC Curve=1.000; Correct Classification Rate=100%; n=192 Rank Sensitivity Phase Transition N0---N12 1 1199 Thrombocytes/Cancer Cells Eosinophils/Cancer Cells Healthy Cells/Cancer Cells Stick Neutrophils/Cancer Cells Lymphocytes/Cancer Cells Segmented Neutrophils/Cancer Cells 2 3 4 5 6 7 637 474 437 376 372 333 Erythrocytes/Cancer Cells 8 299 Monocytes/Cancer Cells Leucocytes/Cancer Cells 9 10 261 159
  • 13. Results of Bootstrap Simulation in Prediction of Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (n=156): Significant Factors (Number of Samples=3333) Rank Kendal Tau-A P< Prothrombin Index 1 -0.209 0.001 Phase Transition N0---N12 2 -0.176 0.01 Glucose 3 0.133 0.05 Weight 4 0.125 0.05 Erythrocytes/Cancer Cells 5 0.124 0.05 Age 6 -0.118 0.05 Heparin Tolerance 7 -0.118 0.05 Healthy Cells/Cancer Cells 8 0.117 0.05 Monocytes/Cancer Cells 9 0.117 0.05 Eosinophils/Cancer Cells 10 0.115 0.05 ESS 11 -0.112 0.05 Erythrocytes tot. 12 0.112 0.05
  • 14. Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (n=156):
  • 16. Prognostic Equation Models of Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (n=156):
  • 17. Prognostic SEPATH-Model of Lung Cancer Patients Survival after Combined Lobectomies/Pneumonectomies (n=156):
  • 18. Conclusion: 5-Year Survival of Local Advanced Non- Small Cell Lung Cancer Patients after Combined Radical Lobectomies and Pneumonectomies Significantly Depended on: 1) Phase Transition N0--N12; 2) Cell Ratio Factors; 3) Blood Cell Circuit; 4) Biochemical Factors; 5) Adjuvant Chemoimmunoradiotherapy; 6) Cancer Characteristics ; 7) Anthropometric Data.
  • 19. Conclusion: Optimal Strategies for Local Advanced Non-Small Cell Lung Cancer Patients are: 1) Availability of Very Experienced Thoracic Surgeons because of Complexity Radical Procedures; 2) Aggressive En Block Surgery and Adequate Lymph Node Dissection for Completeness; 3) Precise Prediction; 4) Adjuvant Chemoimmunoradiotherapy for Lung Cancer Patients with Unfavorable Prognosis.
  • 20. Address: Oleg Kshivets, M.D., Ph.D. Consultant Thoracic, Abdominal, General Surgeon & Surgical Oncologist