Download - Kshivets O. Lung Cancer Surgery
5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS AFTER RADICAL SURGERY SIGNIFICANTLY DEPENDED ON PHASE TRANSITION “EARLY-INVASIVE
CANCER”, LYMPH NODE METASTASES AND CELL RATIO FACTORS
Oleg Kshivets, MD, PhDSiauliai Public Hospital, Siauliai, Lithuania
Abstract• 5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS AFTER
RADICAL SURGERY SIGNIFICANTLY DEPENDED ON PHASE TRANSITION “EARLY-INVASIVE CANCER”, LYMPH NODE METASTASES AND CELL RATIO FACTORS
• Oleg Kshivets• Surgery Department, Siauliai Public Hospital, Lithuania• • OBJECTIVE: We examined factors associated with low/high-risk of generalization of lung cancer (LC) (T1-4N0-2M0)
after complete (R0) lobectomies/pneumonectomies. METHODS: We analyzed data of 602 consecutive LC patients (LCP) (age=57.5±8.1 years; tumor size=4.4±2.3 cm) radically operated and monitored in 1985-2010 (m=536, f=66; pneumonectomies=222, lobectomies=380, combined procedures with resection of pericardium, atrium, aorta, VCS, carina, diaphragm, esophagus, liver, chest wall, ribs, etc.=155; squamous cell carcinoma=367, adenocarcinoma=192, large cell carcinoma=43; T1=215, T2=232, T3=114, T4=41; N0=377, N1=118, N2=107; G1=150, G2=180, G3=272; early LC: LC till 2 cm in diameter with N0=110, invasive LC=492) was reviewed. Variables selected for 5-year survival (5YS) study were input levels of blood cell subpopulations, TNMG, tumor size. Survival curves were estimated by Kaplan-Meier method. Differences in curves between groups were evaluated using a log-rank test. Neural networks computing, multivariate Cox regression, clustering, discriminant analysis, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity.
• RESULTS: Overall life span (LS) was 1973.4±1466.8 days and cumulative 5YS reached 67.9%, 10 years – 59.2%, 20 years – 29.9%. 371LCP lived more than 5 years without LC. 186LCP died because of LC. Cox modeling displayed (Chi2=171.3, df=6, P=0.000) that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0--N1-2, cell ratio factors (CRF) (ratio between cancer cells – CC and blood cells subpopulations) (P=0.000-0.011). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0--N1-2 (rank=2), erythrocytes/CC, healthy cells/CC, thrombocytes/CC, segmented neutrophils/CC,monocytes/CC,leucocytes/CC, stab neutrophils/CC, lymphocytes/CC,eosinophils/CC. Correct prediction of 5YS was 100% by neural networks computing.
• CONCLUSIONS:5YS of LCP after radical procedures significantly depended on: 1) PT “early-invasive LC”; 2) PT N0--N1-2; 3) CRF.
Data
• Males……………………………………………536• Females………….………………………………66• Age=57.5±8.1 years• Tumor Size=4.4±2.3 cm• Pneumonectomies.………………………......222• Bi/lobectomies……………………………..….380• Combined procedures with resection of
pericardium, atrium, aorta, VCS, carina, diaphragm, esophagus, liver, chest wall,
• ribs, etc………..……………………….………155
Staging
• T1……215 N0..…..377 G1..………150• T2……232 N1……118 G2…..……180• T3……114 N2……107 G3.….……272• T4……..41• Early Lung Cancer….………………………...110• Invasive Lung Cancer...................................492• Right..…………………………………………...327• Left………………………………………………275• Adenocarcinoma……………………………...192• Squamous Cell Carcinoma……..…………...367• Large Cell Carcinoma..……………………......43
Survival Rate
• 5-Year Survivors…………..…….371 (61.6%)
• Losses………………………….…186 (30.9%)
• General Life Span=1973.4±1466.8 days
• For 5-Year Survivors=2844.0±1195.7 days
• For Losses=562.5±378.0 days
• Cumulative 5-Year Survival………….67.9%
• Cumulative 10-Year Survival…..........59.2%
General Lung Cancer Patients Survival after Complete Procedures (Kaplan-Meier) (n=602)
Early and Invasive Lung Cancer Patients Survival after Complete Procedures (Kaplan-Meier) (n=602)
Survival of Lung Cancer Patients with N0 and N1-2 after Complete Procedures (Kaplan-Meier) (n=602)
Results of Cox Regression Modeling in Prediction of Lung Cancer
Patients Survival after Complete Procedures (n=602)
Overall Chi2=171.3; df=6; P=0.000;
• Factors Wald df P•• Phase Transition Early-Invasive LC 9.987 1 0.001578 • Phase Transition N0—N1-2 53.682 1 0.000000• Leucocytes/Cancer Cells 16.914 1 0.000039
Stab Neutrophils/Cancer Cells 6.346 1 0.011768• Segmented Neutrophils/Cancer Cells 17.891 1 0.000023• Lymphocytes/Cancer Cells 8.918 1 0.002826
Results of Discriminant Analysis in Prediction of Lung Cancer Patients Survival after Complete Procedures (n=557)
• Discriminant Function Analysis Summary
• Wilks' Lambda: 0.759 approx. F (3,553)=58.533 p< 0.0000;
• Correct Classification Rate=75%
• Wilks'-Lambda P
• Phase Transition Early-Invasive Lung Cancer 0.779 0.000140
• Phase Transition N0—N1-2 0.867 0.000000
• Eosinophils/Cancer Cells 0.775 0.000726
Results of Multi-Factor Clustering of Clinicopathological Data in Prediction of Lung Cancer Patients Survival after Complete
Procedures (n=557)
Results of Clustering in Prediction of Lung Cancer Patients Survival after Complete Procedures
(n=557)
• Logical Formulas based on Simple Mean
• 5-Year Survivors• Early Cancer (11.2%) &• 0.99 <= Erythrocytes/Cancer Cells (10.6%) <= 26.21 &• 4.17 <= Healthy Cells/Cancer Cells (10.7%) <= 78.00 &• N0 (8.8%) & also no N12 (14.7%)• LCP 371 Error1 = 0.71 (265) Error2 = 0.01 (1)• ───────────────────────────────────────────────────────
Losses• Invasive Cancer (11.2%) &• 0.93 <= Erythrocytes/Cancer Cells (10.6%) <= 10.98 &• 3.33 <= Healthy Cells/Cancer Cells (10.7%) <= 35.65 &• no N0 (8.8%) & or N12 (14.7%)• LCP 186 Error1 = 0.33 (61) Error = 0.22 (81)
Neural Networks in Prediction of Lung Cancer Patients Survival after Complete Procedures (n=557)
5-Year Survivors Losses
Baseline Errors=0.000 Total 371 186Area under ROC Curve=1.0 Correct 371 186Correct Classification Rate=100% Wrong 0 0
Results of Neural Networks Computing in Prediction of Lung Cancer Patients Survival after Complete Procedures (n=557)
Error=0.000; Area under ROC Curve=1.00; Correct Classification Rate=100%
Factor Rank Sensitivity
• Phase Transition Early-Invasive LC 1 149776.4
• Phase Transition N0---N12 2 83185.8
• Erythrocytes/Cancer Cells 3 27099.1
• Healthy Cells/Cancer Cells 4 9551.3
• Thrombocytes/Cancer Cells 5 3664.4
• Segmented Neutrophils/Cancer Cells 6 1419.9
• Monocytes/Cancer Cells 7 679.3
• Leucocytes/Cancer Cells 8 590.9
• Stab Neutrophils/Cancer Cells 9 354.0
• Lymphocytes/Cancer Cells 10 140.5
• Eosinophils/Cancer Cells 11 78.2
Results of Genetic Algorithm Selection in Prediction of Lung Cancer Patients Survival after Complete Procedures (n=557)
Factor Useful for 5-Year Survival
• Phase Transition Early-Invasive Lung Cancer YesPhase Transition N0---N12 Yes
• Eosinophils/Cancer Cells Yes• Lymphocytes/Cancer Cells Yes• Monocyte/Cancer Cells Yes• Healthy Cells/Cancer Cells Yes
Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Lung Cancer Patients Survival after Complete Procedures
(n=557)
Results of Bootstrap Simulation in Prediction of Lung Cancer Patients
Survival after Complete Procedures (n=557)
• Number of Samples=3333• Significant Factors Rank Kend.Tau-A P• Phase Transition N0—N12 1 -0.200 0.000• Healthy Cells/Cancer Cells 2 0.152 0.000• Erythrocytes/Cancer Cells 3 0.151 0.000• Thrombocytes/Cancer Cells 4 0.144 0.000• Lymphocytes/Cancer Cells 5 0.133 0.000• Leucocytes/Cancer Cells 6 0.132 0.000• Phase Transition Early-Invas. LC 7 0.125 0.000• Eosinophils/Cancer Cells 8 0.118 0.000• Monocytes/Cancer Cells 9 0.113 0.000• Segm. Neutrophils/Cancer Cells 10 0.084 0.003
Ratio of Lymphocytes and Erythrocytes to Cancer Cells & Glucose Level in Prediction of Lung Cancer Patients Survival after Complete
Procedures (n=557)
Prognostic SEPATH-Model of Lung Cancer Patients Survival after Complete Procedures (n=557)
Lung Cancer Dynamics
Conclusions:
• 5-year survival and life span of lung cancer patients after complete procedures significantly depended on:
• 1) phase transition early—invasive lung cancer;• 2) phase tranzition N0---N12;• 3) cell ratio factors: ratio of cancer cell population to
blood cell subpopulations in integral patient organism.
Address:Oleg Kshivets M.D., Ph.D.,
Consultant Thoracic, Abdominal, General Surgeon & Surgical Oncologist
• Skype: okshivets Tel. 37060878390• e-mail: [email protected], [email protected]• http://myprofile.cos.com/Kshivets• http://youtube.com/user/Kshivets002• http://www.slideshare.net/Kshivets