Gastric Cancer: System Approach

1. 21WCGIC
Poster
presented at:
Gastric Cancer: System Approach
Kshivets Oleg Surgery Department, Roshal Hospital, Roshal, Moscow, Russia
OBJECTIVE: Search of optimal diagnosis and treatment strategies for gastric cancer
(GC) patients (GCP) (T1-4N0-2M0) realized.
METHODS: We analyzed data of 788 consecutive GCP (age=57±9.4 years; tumor
size=5.4±3.1 cm) radically operated (R0) and monitored in 1975-2019 (m=550, f=238; distal
gastrectomies=460, proximal gastrectomies=163, total gastrectomies=165, combined
gastrectomies with resection of pancreas, liver, diaphragm, colon transversum, esophagus,
duodenum, splenectomy, small intestine, kidney, adrenal gland=241; D2-
lymphadenectomy=513, D3-4=275; T1=235, T2=219, T3=179, T4=155; N0=432, N1=108,
N2=248; G1=222, G2=161, G3=405; early GC=162, invasive=626; only surgery=620,
adjuvant chemoimmunotherapy-AT=168 (5-FU + thymalin/taktivin). 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 2136.6±2311.4 days and cumulative 5-year
survival (5YS) reached 58.4%, 10 years – 52.3%, 20 years – 40.3%. 314 GCP lived more
than 5 years (LS=4323.2±2297.4 days), 171 GCP – more than 10 years
(LS=5855.4±2083.6 days). 286 GCP died because of GC (LS=650.7±345.1 days). AT
significantly improved 5YS (69% vs. 56.4%) (P=0.0176 by log-rank test). Cox modeling
displayed that 5YS of GCP 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), G, AT, procedure type, blood cell circuit, prothrombin
index, hemorrhage time, residual nitrogen, ESS, gender (P=0.000-0.046). Neural networks,
genetic algorithm selection and bootstrap simulation revealed relationships between 5YS
and PT early-invasive GC (rank=1), PT N0—N12 (rank=2), healthy cells/CC (3);
erythrocytes/CC (4), thrombocytes/CC (5), glucose (6), prothrombin index (7);
monocytes/CC (8), lymphocytes/CC (9), eosinophils/CC (10), stick neutrophils/CC (11),
segmented neutrophils/CC (12), leucocytes/CC (13). Correct prediction of 5YS was 100%
by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: Survival outcomes 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) procedure type;
10) anthropometric data. Optimal diagnosis and treatment strategies for GC are: 1)
screening and early detection; 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.
P-143
Cox Proportional Hazards Results, n=788
Parameter
Estimate
Standard
Error
Chi-
square
P value
95%
Lower CL
95%
Upper CL
Hazard
Ratio
ESS -0.012758 0.005051 6.38089 0.011536 -0.02266 -0.002859 0.987323
Hemorrhage Time 0.001282 0.000382 11.27865 0.000784 0.00053 0.002031 1.001283
Residual Nitrogen 0.046850 0.009246 25.67652 0.000000 0.02873 0.064972 1.047965
Prothrombin Index 0.020024 0.005074 15.57157 0.000079 0.01008 0.029969 1.020225
Phase Transition N0—N12 0.843907 0.129833 42.24932 0.000000 0.58944 1.098374 2.325434
Gender 0.329383 0.125060 6.93693 0.008443 0.08427 0.574495 1.390110
Operation Type 0.149964 0.075202 3.97667 0.046135 0.00257 0.297358 1.161793
Adjuvant Chemoimmunotherapy -0.619714 0.183454 11.41118 0.000730 -0.97928 -0.260152 0.538098
Phase Transition Early GC—Invasive GC 0.747383 0.298512 6.26851 0.012290 0.16231 1.332455 2.111467
Segmented Neutrophils (tot) 0.844260 0.355982 5.62466 0.017710 0.14655 1.541971 2.326255
Lymphocytes (tot) 0.799475 0.355328 5.06234 0.024451 0.10305 1.495904 2.224372
Segmented Neutrophils/Cancer Cells -0.079159 0.031775 6.20620 0.012730 -0.14144 -0.016881 0.923893
Eosinophils (tot) 0.878755 0.358639 6.00373 0.014276 0.17584 1.581675 2.407901
Stick Neutrophils (tot) 0.761365 0.357698 4.53056 0.033295 0.06029 1.462441 2.141197
Leucocytes (tot) -0.827333 0.355348 5.42068 0.019900 -1.52380 -0.130864 0.437214
Monocytes (tot) 0.930051 0.368213 6.37993 0.011542 0.20837 1.651734 2.534638
G1-3 0.136446 0.067229 4.11909 0.042402 0.00468 0.268213 1.146193
Bootstrap Simulation Rank Kendall’Tau-A P<
Healthy Cells/Cancer Cells 1 0.240 0.000
Tumor Size 2 -0.234 0.000
Leucocytes/Cancer Cells 3 0.228 0.000
PT N0---N12 4 -0.227 0.000
Erythrocytes/Cancer Cells 5 -0.217 0.000
Residual Nitrogen 6 -0.217 0.000
Lymphocytes/Cancer Cells 7 0.216 0.000
T1-4 8 -0.214 0.000
Segmented Neutrophils/Cancer Cells 9 0.211 0.000
Thrombocytes/Cancer Cells 10 0.206 0.000
Hemorrhage Time 11 -0.199 0.000
PT Early---Invasive Cancer 12 -0.192 0.000
Monocytes/Cancer Cells 13 0.147 0.000
Tumor Growth 14 -0.133 0.000
G1-3 15 -0.117 0.001
Localization 16 -0.116 0.000
Chlorides 17 0.105 0.001
Histology 18 -0.084 0.01
Operation Type 19 -0.083 0.01
Combined Operation 20 0.064 0.05
Prothrombin Index 21 -0.055 0.05
Glucose 22 0.054 0.05
Neural Networks: Baseline Error=0.000
Area under ROC Curve=1.000
Correct Classification Rate=100%, n=600
Rank Sensitivity
Phase Transition Early-Invasive Cancer
Phase Transition N0-N12
Healthy Cells/Cancer Cells
Erythrocytes/Cancer Cells
Thrombocytes/Cancer Cells
Glucose
Prothrombin Index
Monocytes/Cancer Cells
Lymphocytes/Cancer Cells
Eosinophils/Cancer Cells
Stick Neutrophils/Cancer Cells
Segmented Neutrophils/Cancer Cells
Leucocytes/Cancer Cells
1
2
3
4
5
6
7
8
9
10
11
12
13
27747
18185
16386
10503
6864
4610
4542
4431
3744
3539
2974
2803
2430
Survival Function
5-Year Survival=58.4%; 10-Year Survival=52.3%;
20-Year Survival=40.3%; n=788; T1-4N0-2M0
Complete Censored
-5 0 5 10 15 20 25 30 35 40
Years after Gastrectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of Early Gastric Cancer Patients=97.2%;
5-Year Survival of Invasive Gastric Cancer Patients=47%; P=0.000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Gastrectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Invasive GCP=626
Early GCP=162
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of GCP with N0=76.5;
5-Year Survival of GCP with N1-2=34.9%, P=0.000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Gastrectomies
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
GCP with N1-2=356
GCP with N0=432
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of GCP after Adjuvant Treatment=69%;
5-Year Survival of GCP after Surgery=56.4%, P=0.0176 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Gastrectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Only Surgery, n=620
Adjuvant Chemoimmunotherapy, n=168
143--P
Oleg Kshivets DOI: 10.3252/pso.eu.21wcgic.2019
Clinical Gastric Cancer