Artificial Intelligence, Synergetics, Complex System Analysis and Simulation of Alive Supersystems for Optimal Management of Local Advanced Lung Cancer
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This document discusses a study on local advanced lung cancer patients (stage t3-4) and their 5-year survival rates following radical surgeries. It analyzes data from various patients to identify factors that significantly impact survival, including tumor characteristics, blood cell ratios, and treatment types, yielding a 62.4% cumulative 5-year survival rate. The study concludes that optimal treatment strategies require experienced thoracic surgeons and effective treatment plans tailored to individual patient conditions.
Artificial Intelligence, Synergetics, Complex System Analysis and Simulation of Alive Supersystems for Optimal Management of Local Advanced Lung Cancer
- 1. Artificial Intelligence, Synergetics, Complex System Analysis and Simulation of Alive Supersystems for Optimal Management of Local Advanced Lung Cancer Kshivets Oleg Surgery Department, Bagrationovsk Hospital, Bagrationovsk, Kaliningrad, Russia
- 2. ABSTRACT 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 top 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 198 consecutive LCP (age=58.1±8.2 years; tumor size=6.8±2.6 cm) radically operated and monitored in 1985-2024 (m=173, f=25; bi/lobectomies=84, pneumonectomies=114, mediastinal lymph node dissections=198; combined LP with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=198; only surgery-S=117, adjuvant chemoimmunoradiotherapy-AT=81: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T3=137, T4=61; N0=94, N1=44, N2=60, M0=198; G1=42, G2=53, G3=103; squamous=118, adenocarcinoma=65, large cell=15, central=115, peripheral=83. Multivariate Cox modeling, clustering, SEPATH, Monte Carlo, synergetics, bootstrap and neural networks computing were used to determine any significant dependence. RESULTS: Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/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, LC cell dynamics, blood cell circuit, cell ratio factors, biochemical factors, hemostasis system, anthropometric data, adjuvant treatment and procedure type. 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………………………………………………….......173 • Females………..……………………………....................25 • Age=58.1±8.2 years • Tumor Size=6.8±2.6 cm • Only Surgery.……………………………………...........117 • Adjuvant Chemoimmunoradiotherapy(CAV/gemzar+ cisplatin+thymalin/taktivin, 5-6 cycles+Radiotherapy • 45-50Gy)……………………….......................................81
- 4. :Radical Procedures • Bi/Lobectomies (R0)……………………………………….…..84 • Pneumonectomies (R0)………...........................................114 • Combined Lobectomies/Pneumonecomies with Resection • of Carina, Trachea, Atrium, Aorta, Vena Cava Superior, Liver, Diaphragm, Pericardium, Vena Azygos, Ribs, Esophagus (R0)……………................................................198 • Mediastinal Lymph Node Dissection………..…………….198
- 5. Staging: • T3……137 N0..…...94 G1……….….42 • T4……..61 N1….....44 G2……….….53 • M0…..198 N2….....60 G3…………103 • Adenocarcinoma………………………….…..65 • Squamos Cell Carcinoma……………….….118 • Large Cell……….....…………………..............15
- 6. Survival Rate: • Alive……………………………………….......119 (60.1%) • 5-Year Survivors…………..…………..……...94 (47.5%) • 10-Year Survivors………………………….....22 (11.1%) • Losses………………………………………….67 (33.8%) • General Life Span=1671.7±1721.6 days • For 5-Year Survivors=2958.6±1723.6 days • For 10-Year Survivors=5571±1841.8 days • For Losses=471.9±344 days • Cumulative 5-Year Survival……………………….62.4% • Cumulative 10-Year Survival…………………......50.4% • Cumulative 20-Year Survival…………………......44.6%
- 7. General Lung Cancer Patients (T3-4) Survival after Complete Combined Lobectomies/Pneumon- ectomies (Kaplan-Meier) (n=198): Survival Function 5YS=62.4%; 10YS=50.4%; 20YS=44.6%. Complete Censored -5 0 5 10 15 20 25 30 Years after Surgery 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 Cumulative Proportion Surviving
- 8. Results of Univariate Analysis of Phase Transition N0—N1-2 in Prediction of Lung Cancer Patients (T3-4) Survival (n=198): Cumulative Proportion Surviving (Kaplan-Meier) 5YS LCP with N0=74.5%; 5YS LCP wih N1-2=50.7% P=0.00086. Complete Censored 0 5 10 15 20 25 30 35 Years after Surgery 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Cumulative Proportion Surviving N12 N0
- 9. Results of Univariate Analysis of Adjuvant Treatment (Adjuvant Chemoimmunoradiotherapy vs Surgery along) in Prediction of Lung Cancer Patients (T3-4) Survival (n=198): Cumulative Proportion Surviving (Kaplan-Meier) 5YS LCP after AT=74.5%; 5YS LCP after Surgery along=55% P=0.00195. Complete Censored 0 5 10 15 20 25 30 35 Years after Surgery 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
- 10. Results of Cox Regression Modeling in Prediction of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumon- ectomies (n=198): Cox Regression, n=198 Parameter Estimate Standard Error Chi- square P value 95% Lower CL 95% Upper CL T3-4 0.93365 0.314224 8.82851 0.002966 0.31778 1.54951 N0---N12 0.61808 0.156019 15.69404 0.000074 0.31229 0.92387 LC Cell Dynamics 0.29571 0.069786 17.95520 0.000023 0.15893 0.43249 Eosinophils (abs) 17.67339 4.625182 14.60098 0.000133 8.60820 26.73858 Prothrombin Index 0.04784 0.015436 9.60378 0.001942 0.01758 0.07809 Protein 0.04103 0.016873 5.91247 0.015034 0.00796 0.07410 Recalcification Time -0.00720 0.003105 5.37561 0.020420 -0.01329 -0.00111 Heparin Tolerance 0.00420 0.001189 12.47949 0.000411 0.00187 0.00653 Adjuvant Chemoimmunoradiotherapy -0.76183 0.354651 4.61434 0.031706 -1.45693 -0.06672 Thrombocytes/Cancer Cells 0.00870 0.002040 18.18890 0.000020 0.00470 0.01270 Eosinophils (tot) -3.65060 0.972359 14.09531 0.000174 -5.55638 -1.74481 Lymphocytes (tot) -0.08709 0.038280 5.17614 0.022899 -0.16212 -0.01206 Pneumonectomies/Lobectomies -0.63257 0.261220 5.86418 0.015452 -1.14455 -0.12059
- 11. Results of Neural Networks and Monte Carlo Computing in Prediction of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumon- ectomies (n=192): Corect Classification Rate=100% Error=0.000 Area under ROC Curve=1.000 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
- 12. Results of Bootstrap Simulation in Prediction of Lung Cancer Patients Survival (T3-4) after Complete Lobectomies/Pneumonectomies (n=192): 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
- 13. Results of Kohonen Self- Organizing Neural Networks Computing in Prediction of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 14. Lung Cancer Cell Dynamics:
- 15. Prognostic Equation Models of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 16. Prognostic Equation Models of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 17. Prognostic Equation Models of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 18. Prognostic Equation Models of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 19. Prognostic Equation Models of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 20. Prognostic Equation Models of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 21. SEPATH Modeling in Prediction of Lung Cancer Patients (T3-4) Survival after Complete Lobectomies/Pneumonectomies (n=192):
- 22. 5YS of local advanced non-small cell LCP (T3-4) after combined radical procedures significantly depended on: 1) tumor characteristics; 2) LC cell dynamics; 3) blood cell circuit; 4) cell ratio factors; 5) biochemical factors; 6) hemostasis system; 7) anthropometric data; 8) adjuvant treatment; 9) procedure type. Conclusion:
- 23. Optimal Strategies for Local Advanced LCP (T3-4) are: 1) Availability of Sufficient Quantity of Experienced Thoracic Surgeons because of Complexity of Radical Procedures; 2) Aggressive En Block Surgery and Adequate Lymph Node Dissection for Completeness; 3) Precise Prediction; 4) AT for LCP with Unfavorable Prognosis. Conclusion:
- 24. 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