Kshivets yokohama iaslc2017
287 likes4,068 views
This study analyzed data from 708 lung cancer patients who underwent surgery to determine optimal diagnosis and treatment strategies. Overall survival was 71.1% at 5 years and decreased to 63% at 10 years and 43.4% at 20 years. Adjuvant chemoimmunoradiotherapy significantly improved 5-year survival for patients with lymph node involvement. Neural network modeling revealed that 5-year survival was most dependent on the phase transition between early and invasive cancer, lymph node status, and various cell ratio factors. The optimal diagnosis and treatment strategies identified were early screening and detection, experienced surgeons, aggressive surgery with lymph node dissection, precise prediction modeling, and adjuvant therapy for high-risk patients.
Kshivets yokohama iaslc2017
- 1. Lung Cancer: System Approach Oleg Kshivets, MD, PhD Surgery Department, Roshal Hospital, Roshal, Moscow, Russia OBJECTIVE: Search of optimal diagnosis and treatment strategies for non-small cell lung cancer (LC) patients (LCP) (T1-4N0- 2M0) was realized. METHODS: We analyzed data of 708 consecutive LCP (age=57.5±8.3 years; tumor size=4.3±2.4 cm) radically operated (R0) and monitored in 1985-2017 (m=613, f=95;lobectomies=461, pneumonectomies=247, mediastinal lymph node dissection=708; combined procedures with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=192; only surgery-S=563, adjuvant chemoimmunoradiotherapy-AT=145: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45- 50Gy; T1=269, T2=251, T3=131, T4=57; N0=460, N1=130, N2=118, M0=708; G1=178, G2=216, G3=314; squamous=394, adenocarcinoma=266, large cell=48; early LC=164, invasive LC=544. 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 2196.3±1764.1 days and cumulative 5-year survival (5YS) reached 71.1%, 10 years – 63%, 20 years – 43.4%. 451LCP lived more than 5 years (LS=3125.7±1560.3 days), 128LCP – more than 10 years (LS=5123.1±1547.9 days).195 LCP died because of LC (LS=560±372.1 days). AT significantly improved 5YS (58.3% vs. 34.1%) (P=0.001 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS 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, RH, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time, weight (P=0.000-0.030). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12(rank=2),healthy cells/CC (3), lymphocytes/CC (4), thrombocytes/CC (5), eosinophils/CC (6), erythrocytes/CC (7), segmented neutrophils/CC (8), glucose (9), monocytes/CC (10), stick neutrophils/CC (11), leucocytes/CC (12). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0). CONCLUSIONS: 5YS 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. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracoabdominal 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. Cox Regression: n=708 Parameter Estimate Standard Error Chi-square P value 95% Lower CL 95% Upper CL Hazard Ratio Weight -0.03847 0.009494 16.41380 0.000051 -0.05707 -0.019857 0.962265 Rh-factor 0.46842 0.210741 4.94059 0.026233 0.05538 0.881470 1.597475 Histology 0.28926 0.085602 11.41872 0.000727 0.12149 0.457039 1.335442 G1-3 0.34479 0.088371 15.22237 0.000096 0.17158 0.517989 1.411688 Glucose -0.30720 0.081717 14.13231 0.000170 -0.46736 -0.147036 0.735504 Prothrombin Index 0.02908 0.006817 18.19131 0.000020 0.01572 0.042439 1.029504 Recalcification Time -0.00522 0.001705 9.39082 0.002181 -0.00857 -0.001883 0.994789 Heparin Tolerance 0.00366 0.000672 29.69991 0.000000 0.00234 0.004979 1.003669 Phase Transition Early—Invasive Cancer -1.74787 0.398789 19.21033 0.000012 -2.52949 -0.966263 0.174144 Adjuvant Chemoimmunoradiotherapy -1.10726 0.204380 29.35098 0.000000 -1.50784 -0.706684 0.330463 Thrombocytes/Cancer Cells -0.00401 0.001847 4.71895 0.029832 -0.00763 -0.000392 0.995997 Eosinophils/Cancer Cells -0.88030 0.403518 4.75925 0.029141 -1.67118 -0.089422 0.414657 Lymphocytes/Cancer Cells -0.25257 0.074446 11.51021 0.000692 -0.39848 -0.106660 0.776800 Healthy Cells/Cancer Cells 0.08529 0.030272 7.93770 0.004842 0.02596 0.144619 1.089030 Thrombocytes (tot) 0.00149 0.000383 15.25088 0.000094 0.00074 0.002244 1.001495 Phase Transition N0---N12 1.16358 0.148822 61.13067 0.000000 0.87190 1.455267 3.201377 Neural Networks: n=646; Baseline Error=0.000; Area under ROC Curve=1.000; Correct Classification Rate=100% Rank Sensitivity Phase Transition Early---Invasive Cancer 1 31912 Phase Transition N0---N12 2 23902 Healthy Cells/Cancer Cells 3 2324 Lymphocytes/Cancer Cells 4 10104 Thrombocytes/Cancer Cells 5 9822 Eosinophils/Cancer Cells 6 9448 Erythrocytes/Cancer Cells 7 8308 Segmented Neutrophils/Cancer Cells 8 8289 Glucose 9 7268 Monocytes/Cancer Cells 10 5583 Stick Neutrophils/Cancer Cells 11 5285 Leucocytes/Cancer Cells 12 3871 Bootstrap Simulation Rank Kendall’Tau- A P< Healthy Cells/Cancer Cells 1 -0.229 0.000 Erythrocytes/Cancer Cells 2 -0.225 0.000 Lymphocytes/Cancer Cells 3 -0.220 0.000 Thrombocytes/Cancer Cells 4 -0.202 0.000 PT N0---N12 5 0.200 0.000 Leucocytes/Cancer Cells 6 -0.189 0.000 Tumor Size 7 0.158 0.000 Prothrombin Index 8 0.154 0.000 Eosinophils/Cancer Cells 9 -0.148 0.000 PT Early---Invasive Cancer 10 -0.146 0.000 Monocytes/Cancer Cells 11 -0.140 0.000 Segmented Neutrophils/Cancer Cells 12 -0.138 0.000 T1-4 13 0.137 0.000 Weight 14 -0.098 0.000 Segmented Neutrophils (%) 15 0.098 0.001 Erythrocytes (tot) 16 -0.092 0.000 G1-3 17 0.085 0.001 ESS 18 0.085 0.001 Lymphocytes (tot) 19 -0.082 0.01 Lymphocytes (%) 20 -0.078 0.01 Only Surgery 21 -0.073 0.01 Glucose 22 -0.072 0.01 Heparin Tolerance 23 0.067 0.05 Eosinophils (%) 24 -0.057 0.05 Procedures Type 25 -0.055 0.05