CONCLUSIONS: 5YS of local advanced ECP after combined radical procedures significantly depended on: tumor characteristics, blood cell circuit, cell ratio factors, biochemical factors, hemostasis system, anthropometric data and adjuvant treatment. Optimal strategies for local advanced ECP are: 1) availability of very experienced thoracoabdominal surgeons because of complexity radical procedures; 2) aggressive en block surgery and adequate lymph node dissection for completeness; 3) precise prediction; 4) AT for ECP with unfavorable prognos

1. Combined Esophagogastrectomies: Survival Outcomes
in Patients with Local Advanced Esophageal Cancer
Oleg Kshivets, MD, PhD Surgery Department, Roshal Hospital, Roshal, Moscow, Russia
OBJECTIVE: The survival of patients with local advanced of esophageal cancer (EC) takes several months. Radical
operations are extremely complex and remain the prerogative of several best thoracoabdominal surgeons of the
world. The search of optimal treatment plan for EC patients (ECP) with stage T4N0-2M0 was realized. We examined
factors in terms of precise prediction of 5-year survival (5YS) of local advanced ECP after complete (R0) combined
esophagogastrectomies (E).
METHODS: We analyzed data of 153 consecutive ECP (age=54.9±9. years; tumor size=7.8±2.5 cm) radically operated
and monitored in 1975-2020 (m=118, f=35; Lewis=48, Garlock=105, combined E with resection of trachea, bronchus,
lung, aorta, VCS, pericardium, liver, pancreas, diaphragm, colon, splenectomy=153; only surgery-S=99, adjuvant
chemoimmunoradiotherapy-AT=54: 5FU+thymalin/taktivin +radiotherapy 45-50Gy; T4=153; N0=56, N1=17, N2=80,
M0=153; G1=32, G2=23, G3=98; squamous=54, adenocarcinoma=97, mix=2. Variables selected for 5YS 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 ECP were evaluated using a log-rank test. Multivariate
Cox modeling, multi-factor clustering, discriminant analysis, structural equation modeling, Monte Carlo, bootstrap
simulation and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 1518.3±1945.4 days and cumulative 5YS reached 38.9%, 10 years – 26.8%, 20
years – 19.8%. 40 ECP lived more than 5 years (LS=4030.5±2386.8 days), 14 – more than 10 years (LS=6674±2258.5
days). 79 ECP died because of EC (LS=632.3±309.1 days). AT significantly improved 5YS (51.1% vs. 33.9%), AT, age,
blood cells, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), ESS, prothrombin index,
protein (P=0.000-0.040). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships
between 5YS and N0-12 (rank=1), eosinophils/CC (rank=2), stick neutrophils/CC (3), healthy cells/CC (4),
erythrocytes/CC (5), monocytes/CC (6), lymphocytes/CC (7), thrombocytes/CC (8), segmented neutrophils/CC (9),
leucocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing.
CONCLUSIONS: 5YS of local advanced ECP after combined radical procedures significantly depended on: tumor
characteristics, blood cell circuit, cell ratio factors, biochemical factors, hemostasis system, anthropometric data and
adjuvant treatment. Optimal strategies for local advanced ECP are: 1) availability of very experienced
thoracoabdominal surgeons because of complexity radical procedures; 2) aggressive en block
surgery and adequate lymph node dissection for completeness; 3) precise prediction;
4) AT for ECP with unfavorable prognosis.
Neural Networks:
Baseline Error=0.000; Area under
ROC Curve=1.000; Correct
Classification Rate=100%; n=119
Rank Sensitivity
Phase Transition N0---N12 1 701
Eosinophils/Cancer Cells 2 491
Stick Neutrophils/Cancer Cells 3 269
Healthy Cells/Cancer Cells 4 176
Erythrocytes/Cancer Cells 5 175
Monocytes/Cancer Cells 6 151
Lymphocytes/Cancer Cells 7 124
Thrombocytes/Cancer Cells 8 100
Segmented Neutrophils/Cancer Cells 9 30
Leucocytes/Cancer Cells 10 24
Cox Proportional Hazards Results,
ECPT4N0-2M0, n=153
Parameter
Estimate
Standard
Error
Chi2 P value
Leucocytes -14.7695 3.568331 17.13163 0.000035
Monocytes (%) 0.9933 0.194297 26.13352 0.000000
ESS -0.0462 0.016035 8.29704 0.003971
Prothrombin Index 0.0745 0.016092 21.43087 0.000004
Eosinophils (abs) 24.0232 5.699437 17.76637 0.000025
Stick Neutrophils (abs) 11.5798 2.880807 16.15746 0.000058
Segmented Neutrophils (abs) 14.1418 3.858441 13.43337 0.000247
Lymphocytes (abs) 18.2601 4.034686 20.48277 0.000006
Phase Transition N0---N12 1.7942 0.350778 26.16159 0.000000
Age 0.0607 0.014796 16.81244 0.000041
Histology -0.9610 0.299217 10.31426 0.001320
Tumor Growth -0.7728 0.333794 5.36023 0.020601
Stick Neutrophils/Cancer Cells -10.4603 3.448870 9.19888 0.002422
Monocytes/Cancer Cells -11.4366 4.369661 6.85007 0.008864
Esophageal/Cardioesophageal Cancer 1.1047 0.305000 13.11926 0.000292
Eosinophils (%) -0.8866 0.224724 15.56375 0.000080
Segmented Neutrophils/Cancer Cells 1.2604 0.487956 6.67204 0.009794
Lymphocytes (tot) -2.7854 0.649292 18.40364 0.000018
Segmented Neutrophils (tot) -2.0776 0.573809 13.10942 0.000294
Leucocytes (tot) 2.1281 0.517175 16.93226 0.000039
Adjuvant Chemoimmunotherapy -1.4382 0.359631 15.99294 0.000064
G1-3 0.4878 0.167933 8.43792 0.003675
Protein 0.0438 0.019390 5.11383 0.023736
Healthy Cells/Cancer Cells 0.4984 0.231522 4.63402 0.031344
Erythrocytes/Cancer Cells -1.4656 0.604416 5.87966 0.015317
Thrombocytes/Cancer Cells -0.0114 0.005583 4.17846 0.040941
Eosinophils/Cancer Cells -10.6284 4.948386 4.61329 0.031725
Bootstrap Simulation:
Number of Samples=3333
Rank Kendall
Tau
P<
Hemorrhage Time 1 -0.171 0.05
Blood Chlorides 2 0.171 0.05
Esophageal/Cardioesophageal
Cancer 3 -0.151 0.05
Prothrombin Index 4 -0.146 0.05
Phase Transition N0---N12 5 -0.144 0.05
Protein 6 -0.142 0.05
Survival Function
5-Year Survival=38.9%; 10-Year Survival=26.8%; 20-Year Survival=19.8%;
n=153; T4N0-2M0
Complete Censored
-5 0 5 10 15 20 25 30 35
Years after Combined Esophagogastrectomies
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
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP with N0=52.8%; 5-Year Survival of ECP with N1-2=29.2%;
P=0.00072 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30
Years after Combined Esophagogastrectomies
-0.1
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
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival after AT=51.1%; 5-Year Survival after Surgery=33.9%;
P=0.007 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35
Years after Combined Esophagogastrectomies
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
only Surgery=99
AT=54
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP=58.3%; 5-Year Survival of CECP=29.4%;
P=0.00007 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35
Years after Combined Esophagogastrectomies
-0.1
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
ECP=58
CECP=105