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Kshivets iaslc denver2021

Lung Cancer Prognosis and Cell Ratio Factors OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting non-small cell lung cancer (LC) patients (LCP) survival. CRF - ratio between cancer cells (CC) and blood cells subpopulations. Cox modeling displayed that LCP survival significantly depended on CRF: leucocytes/CC, segmented neutrophils/CC, lymphocytes/CC, healthy cells/CC (P=0.000-0.016). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and healthy cells/CC (rank=1), segmented neutrophils/CC (rank=2), erythrocytes/CC (rank=3), thrombocytes/CC (4), leucocytes/CC (5), lymphocytes/CC (6), eosinophils/CC (7), monocytes/CC (8), stick neutrophils/CC (9). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0). CONCLUSIONS: LCP survival after radical procedures significantly depended on CRF.

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Lung Cancer Prognosis and Cell
Ratio Factors
Kshivets Oleg
Roshal Hospital, Roshal, Moscow
Russia
Presenter DISCLOSURES
Ineligible Company
(formerly: Commercial Interest)
Relationship(s)
No No
Abstract
Lung Cancer Prognosis and Cell Ratio Factors
Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia
OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting non-small cell lung cancer (LC) patients (LCP) survival. CRF - ratio
between cancer cells (CC) and blood cells subpopulations.
METHODS: We analyzed data of 768 consecutive LCP (T1-4N0-2M0) (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; right LC=412, left LC=356; central=290; peripheral=478. Variables selected for
prognosis 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 years –
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). Cox modeling displayed that LCP survival significantly depended on CRF: leucocytes/CC, segmented neutrophils/CC,
lymphocytes/CC, healthy cells/CC (P=0.000-0.016). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships
between 5YS and healthy cells/CC (rank=1), segmented neutrophils/CC (rank=2), erythrocytes/CC (rank=3), thrombocytes/CC (4), leucocytes/CC (5),
lymphocytes/CC (6), eosinophils/CC (7), monocytes/CC (8), stick neutrophils/CC (9). Correct prediction of 5YS was 100% by neural networks
computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: LCP survival after radical procedures significantly depended on CRF.
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 Trachea, Carina,
Atrium, Aorta, Vena Cava Superior, Vena Azygos,
Pericardium, Liver, Diaphragm, Ribs, Esophagus…….193
Mediastinal Lymphadenectomy.………………..…...……768
Staging:
T1……..320 N0..……516 G1…………194
T2……..255 N1…......131 G2…………243
T3……..133 N2…......121 G3…………331
T4………60 N1-2…...252 M0…….…...768
Adenocarcinoma………………………………………………………..301
Squamous Cell Carcinoma……………………………………..……..417
Large Cell Carcinoma………………………………………..................50

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Kshivets iaslc denver2021

  • 1. Lung Cancer Prognosis and Cell Ratio Factors Kshivets Oleg Roshal Hospital, Roshal, Moscow Russia
  • 2. Presenter DISCLOSURES Ineligible Company (formerly: Commercial Interest) Relationship(s) No No
  • 3. Abstract Lung Cancer Prognosis and Cell Ratio Factors Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting non-small cell lung cancer (LC) patients (LCP) survival. CRF - ratio between cancer cells (CC) and blood cells subpopulations. METHODS: We analyzed data of 768 consecutive LCP (T1-4N0-2M0) (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; right LC=412, left LC=356; central=290; peripheral=478. Variables selected for prognosis 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 years – 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). Cox modeling displayed that LCP survival significantly depended on CRF: leucocytes/CC, segmented neutrophils/CC, lymphocytes/CC, healthy cells/CC (P=0.000-0.016). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and healthy cells/CC (rank=1), segmented neutrophils/CC (rank=2), erythrocytes/CC (rank=3), thrombocytes/CC (4), leucocytes/CC (5), lymphocytes/CC (6), eosinophils/CC (7), monocytes/CC (8), stick neutrophils/CC (9). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0). CONCLUSIONS: LCP survival after radical procedures significantly depended on CRF.
  • 4. 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
  • 5. Radical Procedures (R0): Upper Lobectomies……….………………………………...277 Lower Lobectomies.….....................................................177 Middle Lobectomies.…………………………..…………….18 Bilobectomies.………………………………..……………....42 Pneumonectomies……………………………..……………254 Combined Procedures with Resection of Trachea, Carina, Atrium, Aorta, Vena Cava Superior, Vena Azygos, Pericardium, Liver, Diaphragm, Ribs, Esophagus…….193 Mediastinal Lymphadenectomy.………………..…...……768
  • 6. Staging: T1……..320 N0..……516 G1…………194 T2……..255 N1…......131 G2…………243 T3……..133 N2…......121 G3…………331 T4………60 N1-2…...252 M0…….…...768 Adenocarcinoma………………………………………………………..301 Squamous Cell Carcinoma……………………………………..……..417 Large Cell Carcinoma………………………………………..................50
  • 7. 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%
  • 8. 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 General Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (Kaplan-Meier) (n=768):
  • 9. 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 Years after Lobectomies/Pneumonectomies -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 Early—Invasive Cancer in Prediction of Lung Cancer Patients Survival (n=768):
  • 10. Cumulative Proportion Surviving (Kaplan-Meier) 10-Year Survival of Lung Cancer Patients with N0=78.3%; 10-Year Survival of Lung Cancer Patients with N1-2=35.2%; P=0.0000 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 Cumulative Proportion Surviving Lung Cancer with N1-2, n=252 Lung Cancer with N0=516 Results of Univariate Analysis of Phase Transition N0—N1-2 in Prediction of Lung Cancer Patients Survival (n=768):
  • 11. Results of Cox Regression Modeling in Prediction of Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (n=768): Cell Ratio Factors, n=768 Parameter Estimate Standard Error Chi- square P value 95% Lower CL 95% Upper CL Hazard Ratio Leucocytes/CC -0.476505 0.139217 11.71515 0.000620 -0.749366 -0.203644 0.620950 Segmented Neutrophils/CC 0.533254 0.151376 12.40947 0.000427 0.236562 0.829946 1.704470 Lymphocytes/CC 0.395129 0.164461 5.77231 0.016281 0.072791 0.717467 1.484576 Healthy Cells/CC -0.039992 0.009692 17.02492 0.000037 -0.058988 -0.020995 0.960797
  • 12. Results of Discriminant Function Analysis in Prediction of Lung Cancer Patients Survival after Complete Lobectomies/Pneumonectomies (n=701): N=701 Discriminant Function Analysis Summary: No. of vars in model: 4; Grouping: SUR5 (2 grps) Wilks' Lambda: .73129 approx. F (4,696)=63.935 p<0.0000 Wilks' Lambda Partial Lambda F-remove (1,696) p-value Toler. 1-Toler. (R-Sqr.) PT N0----N12 0.834783 0.876027 98.49628 0.000000 0.896934 0.103066 Leucocytes/Cancer Cells 0.736380 0.993091 4.84203 0.028102 0.082118 0.917882 Segmented Neutrophils/Cancer Cells 0.735348 0.994484 3.86025 0.049840 0.083382 0.916618 PT Early---Invasive Cancer 0.759831 0.962441 27.16153 0.000000 0.696661 0.303340 N=701 Discriminant Function Analysis Summary: No. of vars in model: 6; Grouping: SUR5 (2 grps) Wilks' Lambda: .88304 approx. F (6,694)=15.320 p< .0000 Wilks' Lambda Partial Lambda F-remove (1,694) p-value Toler. 1-Toler. (R-Sqr.) Erythrocytes/Cancer Cells 0.918245 0.961665 27.66516 0.000000 0.347042 0.652958 Leucocytes/Cancer Cells 0.897282 0.984132 11.19023 0.000867 0.000938 0.999062 Stick Neutrophils/Cancer Cells 0.889808 0.992398 5.31623 0.021422 0.306522 0.693478 Segmented Neutrophils/Cancer Cells 0.898416 0.982890 12.08124 0.000541 0.002170 0.997830 Lymphocytes/Cancer Cells 0.895310 0.986299 9.64051 0.001981 0.007649 0.992351 Monocytes/Cancer Cells 0.894198 0.987525 8.76678 0.003172 0.111689 0.888311
  • 13. 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 Healthy Cells/Cancer Cells 1 14897 Segmented Neutrophils/Cancer Cells Erythrocytes/Cancer Cells Thrombocytes/Cancer Cells 2 3 4 13757 12803 12218 Leucocytes/Cancer Cells Lymphocytes/Cancer Cells Eosinophils/Cancer Cells Monocytes/Cancer Cells Stick Neutrophils/Cancer Cells 5 6 7 8 9 9573 9059 8261 7525 6793
  • 14. 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 Segmented Neutrophils/Cancer Cells 6 0.173 0.000 Monocytes/Cancer Cells 7 0.111 0.000 PT Early—Invasive Cancer 8 0.107 0.000 PT N0---N12 9 -0.092 0.001 Stick Neutrophils/Cancer Cells 10 0.073 0.01 Eosinophils/Cancer Cells 11 0.067 0.05 Results of Bootstrap Simulation in Prediction of Lung Cancer Patients Survival after Lobectomies/Pneumonectomies (n=701):
  • 15. Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Lung Cancer Patients Survival after Lobectomies/Pneumonectomies (n=701):
  • 16. Prognostic Equation Models of Lung Cancer Patients Survival after Lobectomies/Pneumonectomies (n=701):
  • 17. Prognostic Equation Models of Lung Cancer Patients Survival after Lobectomies/Pneumonectomies (n=701):
  • 18. Prognostic SEPATH-Model of Lung Cancer Patients Survival after Lobectomies/Pneumonectomies (n=701):
  • 19. 1. Lung Cancer Patients survival after radical procedures significantly depended on Cell Ratio Factors. 2. Cell Ratio Factors significantly affect phase transition early—invasive cancer and lymph node metastases. Conclusion:
  • 20. 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