Abstract

Objective: 10-Year survival (10YS) after radical surgery for non-small cell lung cancer (LC) pa­tients (LCP) (T1-4N0-2M0) was analyzed. Methods: We analyzed data of 768 consecutive LCP (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; early LC=214, invasive LC=554; right LC=412, left LC=356; central=290; peripheral=478. Variables selected for 10YS 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, 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). AT significantly improved 10YS (52.4% vs. 27.7%) (P=0.00002 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 10YS 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, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time, weight, color index (P=0.000-0.039). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 10YS and PT early-invasive LC (rank=1), thrombocytes/CC (rank=2), PT N0—N12(rank=3), segmented neutrophils/CC (4), healthy cells/CC (5), lymphocytes/CC (6), erythrocytes/CC (7), stick neutrophils/CC (8), eosinophils/CC (9), leucocytes/CC (10), monocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0). Conclusions: 10-Year survival 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; 10) surgery type. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic 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.

Highlights

  • In the world, lung cancer is the number 1 killer today, despite the astronomical efforts of humankind to fight it

  • 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)

  • AT significantly improved 10-Year survival (10YS) (52.4% vs. 27.7%) (P=0.00002 by log-rank test) only for LCP with N1-2

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Summary

Introduction

Lung cancer is the number 1 killer today, despite the astronomical efforts of humankind to fight it. 2.2 million new patients with lung cancer were diagnosed each year, from which 79-90% have already died. Non-small cell lung cancer (LC) is the main cause of death from cancer, and real 5-year survival (5YS) across all stages of the disease is approximately 21% in the USA and 16% in Europe [1,6]. Adjuvant chemotherapy has recently become a new standard of care for patients with LC (LCP) after clinical trials showed approximately 5-15% improvement in overall survival for those with higher risk disease, especially for stage II-IIIA [3,4,5]. In the total population it is known that poor baseline cytotoxic function of patient immune cells correlates with a higher long-term rate of cancer relapses and generalization after radical procedures [8]

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