Abstract
Methods: We analyzed data of 796 consecutive GCP (age=57.1±9.4 years; tumor size=5.4±3.1 cm) radically operated (R0) and monitored in 1975-2021 (m=556, f=240; distal gastrectomies-G=461, proximal G=165, total G=170, D2 lymph node dissection=551; combined G with resection of 1-7 adjacent organs (pancreas, liver, diaphragm, esophagus, colon transversum, splenectomy, small intestine, kidney, adrenal gland, etc.)=245; D3-4 lymph node dissection=245; only surgery-S=623, adjuvant chemoimmunotherapy-AT=173: 5FU+thymalin/taktivin; T1=237, T2=220, T3=182, T4=157; N0=435, N1=109, N2=252, M0=796; G1=222, G2=164, G3=410; early GC=164, invasive GC=632; 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 GCP 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 2130.8±2304.3 days and cumulative 5-year survival (5YS) reached 58.4%, 10 years – 52.4%, 20 years – 40.4%. 316 GCP lived more than 5 years (LS=4316.1±2292.9 days), 169 GCP – more than 10 years (LS=5919.5±2020 days). 294 GCP died because of GC (LS=640.6±347.1 days). AT significantly improved 10YS (62.3% vs. 50.5%) (P=0.0228 by log-rank test) for GCP. Cox modeling displayed that 10YS of LCP significantly depended on: phase transition (PT) early-invasive GC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, AT, blood cell circuit, prothrombin index, hemorrhage time, residual nitrogen, age, sex, procedure type (P=0.000-0.039). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 10YS and healthy cells/CC (rank=1), PT early-invasive GC (rank=2), PT N0—N12(rank=3), erythrocytes/CC (4), thrombocytes/CC (5), monocytes/CC (6), segmented neutrophils/CC (7), eosinophils/CC (8), leucocytes/CC (9), lymphocytes/CC (10), stick neutrophils/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 GCP 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) GC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.
Highlights
Gastric cancer (GC) is the number two killer in the world in the structure of mortality from malignant neoplasms
Overall life span (LS) was 2130.8±2304.3 days and cumulative 5-year survival (5YS) reached 58.4%, 10 years – 52.4%, 20 years – 40.4%. 316 GC patients (GCP) lived more than 5 years (LS=4316.1±2292.9 days), 169 GCP – more than 10 years (LS=5919.5±2020 days)
We developed optimal treatment strategies that incorporate bolus chemotherapy and immunotherapy after radical, aggressive en-block surgery
Summary
Gastric cancer (GC) is the number two killer in the world in the structure of mortality from malignant neoplasms. Information on the 10-year survival rate is extremely important in optimizing the treatment and diagnostic process in oncology and especially for extremely aggressive cancer –GC. The optimal treatment plan in general and optimal approach for adjuvant chemotherapy in particular has not been defined and long-term prognosis of GCP especially with stage III-IV remains poor, because of local relapse and distant metastases, with the real 5-year survival rate after radical procedures only 30-35% [2]. One of the approaches developed involves aggressive en-block surgery and complete lymphadenectomy. Another of the modern approaches developed to enhance the efficacy of surgery is the combination of chemotherapy and immunotherapy or gene therapy which offers the advantage of exposing GC cell population for drugs and immune factors obviating cancer cell-cycle cytotoxic and host-immunoprotective effects [3,4]. We developed optimal treatment strategies that incorporate bolus chemotherapy and immunotherapy after radical, aggressive en-block surgery
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