1.
Survival of Esophageal Cancer Patients was Significantly Superior in
Comparison with Cardioesophageal Cancer Patients after Surgery P39
Oleg Kshivets, MD, PhD Surgery Department, Roshal Hospital, Roshal, Moscow, Russia
OBJECTIVE: This study aimed to determine localization influence of tumor for 5-year survival (5YS) of
esophageal (EC) or cardioesophageal (CC) cancer patients (ECP, CEP) after complete en block (R0)
esophagogastrectomies (EG) through left/right thoracoabdominal incision.
METHODS: We analyzed data of 543 consecutive patients (age=56.4±8.8 years; tumor size=6±3.5 cm)
radically operated (R0) and monitored in 1975-2019 (m=405, f=138; ECP=259, CEP=284;
esophagogastrectomies (EG) Garlock=280, EG Lewis=263, combined EG with resection of pancreas, liver,
diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium, splenectomy=151;
adenocarcinoma=308, squamous=225, mix=10; T1=126, T2=114, T3=178, T4=125; N0=275, N1=69, N2=199;
G1=157, G2=139, G3=247; early EC=107, invasive=436; only surgery=420, adjuvant
chemoimmunoradiotherapy-AT=123: 5-FU+thymalin/taktivin+radiotherapy 45-50Gy). 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 1892.4±2241 days and cumulative 5-year survival (5YS) reached
51.9%, 10 years – 45.7%, 20 years – 33.5%. 183 ECP lived more than 5 years (LS=4311±2419.7 days), 98 ECP –
more than 10 years (LS=5903.4±2299.4 days). 224 died because of EC/CC (LS=629.2±320.1 days). 5YS of ECP
(67.3%, LS=2605±2628.9 days) was significantly superior in comparison with CEP (36.4%, LS=1242.6±1558.5
days) (P=0.00000 by log-rank test). AT significantly improved 5YS (68.2% vs. 48.5%) (P=0.00033 by log-rank
test). Cox modeling displayed that 5YS of ECP/CEP significantly depended on: phase transition (PT) N0—
N12 in terms of synergetics, cell ratio factors (ratio between cancer cells- CC and blood cells
subpopulations), T, G, histology, age, AT, localization, blood cells, prothrombin index, coagulation time,
residual nitrogen, blood group, Rh, glucose, protein (P=0.000-0.008). Neural networks, genetic algorithm
selection and bootstrap simulation revealed relationships between 5YS and healthy cells/CC (rank=1), PT
early-invasive EC (rank=2), PT N0—N12 (rank=3), erythrocytes/CC (4), thrombocytes/CC (5), stick
neutrophils/CC (6), lymphocytes/CC (7), segmented 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: Survival 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) EC characteristics; 9) localization: esophageal cancer—
cardioesophageal cancer; 10) anthropometric data.
Survival Function
General Esophageal Cancer Patients Survival, n=543
5-Year Survival=51.9%; 10-Year Survival=45.7%; 20-Year Survival=33.5%
Complete Censored
-5 0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
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 ECP=100; 5-Year Survival of Invasive ECP=38.5%,
P=0.00000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Invasive ECP, n=436
Early ECP, n=107
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP with N0=73.9%; 5-Year Survival of ECP with N1-2=27.5%
P=0.00000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
ECP with N1-2, n=268
ECP with N0, n=275
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP after Adjuvant Treatment=68.2%;
5-Year Survival of ECP after Surgery alone=48.5%;
P=0.00033 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
Adjuvant Chemoimmunoradiotherapy, n=123
Only Surgery, n=420
Cox Proportional Hazards Results;
ECP/CECP=543;
Factors:
Parameter
Estimate
Standard
Error
Chi-
square
P value
95%
Lower CL
95%
Upper CL
Hazard
Ratio
95%
Hazard
Ratio
Lower CL
95%
Hazard
Ratio
Upper CL
Blood Group 0.24084 0.072842 10.93155 0.000945 0.09807 0.383607 1.272315 1.103040 1.467569
Rh-Factor -0.56749 0.179791 9.96289 0.001597 -0.91988 -0.215110 0.566944 0.398567 0.806453
Hemorrhage Blood 0.00137 0.000411 11.17880 0.000827 0.00057 0.002177 1.001374 1.000568 1.002180
Glucose -0.22903 0.083815 7.46693 0.006284 -0.39330 -0.064756 0.795305 0.674823 0.937296
Residual Nitrogen 0.05126 0.012004 18.23193 0.000020 0.02773 0.074786 1.052594 1.028117 1.077653
Protein 0.02465 0.008997 7.50688 0.006146 0.00702 0.042284 1.024956 1.007041 1.043190
Prothrombin Index 0.01879 0.006672 7.93214 0.004856 0.00571 0.031867 1.018968 1.005730 1.032380
T1-4 0.40958 0.095588 18.35954 0.000018 0.22223 0.596926 1.506179 1.248855 1.816525
N0---N12 0.65015 0.163700 15.77344 0.000071 0.32930 0.970993 1.915823 1.389996 2.640565
Age 0.03171 0.007996 15.72396 0.000073 0.01603 0.047377 1.032214 1.016164 1.048517
Histology -0.34331 0.130570 6.91333 0.008556 -0.59922 -0.087398 0.709419 0.549239 0.916313
G1-3 0.39994 0.089500 19.96816 0.000008 0.22452 0.575354 1.491732 1.251723 1.777760
Adjuvant Chemoimmunoradiotherapy -0.98414 0.202411 23.64005 0.000001 -1.38086 -0.587424 0.373760 0.251362 0.555757
Leucocytes tot -1.40161 0.356959 15.41769 0.000086 -2.10124 -0.701985 0.246200 0.122305 0.495601
Eosinophils tot 1.42230 0.366785 15.03692 0.000105 0.70341 2.141185 4.146644 2.020639 8.509513
Stick Neutrophils tot 1.41661 0.359711 15.50931 0.000082 0.71159 2.121628 4.123112 2.037224 8.344714
Segmented Neutrophils tot 1.42786 0.356560 16.03634 0.000062 0.72901 2.126702 4.169756 2.073034 8.387157
Lymphocytes tot 1.37115 0.358701 14.61190 0.000132 0.66811 2.074194 3.939891 1.950551 7.958130
Monocytes tot 1.31857 0.370179 12.68771 0.000368 0.59303 2.044109 3.738076 1.809469 7.722272
Segmented Neutrophils/Cancer Cells -0.13490 0.045343 8.85118 0.002929 -0.22377 -0.046029 0.873803 0.799498 0.955014
Esophageal Cancer---Cardioesophageal Cancer 0.31674 0.140910 5.05257 0.024589 0.04056 0.592914 1.372640 1.041392 1.809253
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP=67.3%; 5-Year Survival of CECP=36.4%; P=0.000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
CumulativeProportionSurviving
ECP=259
CECP=284
Discriminant Function Analysis Summary:
No. of vars in model=32; n=407
Wilks' Lambda: .39522 approx. F (32,374)=17.885 p<0.0000
Wilks'
Lambda
Partial
Lambda
F-remove
(1,374)
p-value Toler.
1-Toler.
(R-Sqr.)
Hemoglobin 0.405250 0.975248 9.49213 0.002216 0.359799 0.640201
Erythrocytes 0.407808 0.969131 11.91296 0.000621 0.024344 0.975657
Leucocytes 0.413786 0.955129 17.57030 0.000035 0.000405 0.999595
Stick Neutrophils (%) 0.401817 0.983580 6.24345 0.012894 0.081515 0.918486
Segmented Neutrophils (%) 0.412991 0.956969 16.81737 0.000051 0.010315 0.989685
Lymphocytes (%) 0.404156 0.977887 8.45715 0.003853 0.010516 0.989484
Hemorrhage Blood 0.404068 0.978100 8.37382 0.004030 0.843012 0.156988
Residual Nitrogen 0.438737 0.900811 41.18147 0.000000 0.742369 0.257631
Prothrombin Index 0.399773 0.988609 4.30916 0.038590 0.836103 0.163898
Segmented Neutrophils (abs) 0.417926 0.945668 21.48770 0.000005 0.000587 0.999413
Lymphocytes (abs) 0.407544 0.969759 11.66284 0.000708 0.002901 0.997099
T1-4 0.436492 0.905444 39.05685 0.000000 0.541731 0.458269
N0--N12 0.424456 0.931120 27.66664 0.000000 0.704162 0.295838
Weight 0.407512 0.969834 11.63306 0.000719 0.011910 0.988090
G1-3 0.407735 0.969303 11.84421 0.000644 0.835999 0.164001
Tumor Growth 0.407466 0.969943 11.58955 0.000735 0.653263 0.346737
Adjuvant Chemoimmunoradiotherapy 0.400524 0.986755 5.02014 0.025641 0.911147 0.088853
Combined Procedures 0.405038 0.975759 9.29132 0.002466 0.720317 0.279683
Erythrocytes (tot) 0.405575 0.974467 9.79976 0.001883 0.008919 0.991081
Leucocytes (tot) 0.409886 0.964218 13.87926 0.000225 0.000036 0.999964
Eosinophils (tot) 0.405589 0.974434 9.81255 0.001870 0.010102 0.989898
Stick Neutrophils (tot) 0.400922 0.985776 5.39657 0.020712 0.003166 0.996834
Segmented Neutrophils (tot) 0.411970 0.959341 15.85091 0.000082 0.000068 0.999933
Lymphocytes (tot) 0.408867 0.966622 12.91450 0.000370 0.000381 0.999619
Monocytes (tot) 0.407706 0.969373 11.81657 0.000653 0.005423 0.994577
Leucocytes/Cancer Cells 0.401196 0.985102 5.65605 0.017897 0.000009 0.999991
Eosinophils/Cancer Cells 0.401077 0.985396 5.54290 0.019072 0.009880 0.990120
Stick Neutrophils/Cancer Cells 0.401480 0.984406 5.92440 0.015400 0.008813 0.991187
Segmented Neutrophils/Cancer Cells 0.401377 0.984659 5.82676 0.016264 0.000025 0.999975
Lymphocytes/Cancer Cells 0.401133 0.985257 5.59635 0.018507 0.000082 0.999918
Monocytes/Cancer Cells 0.400441 0.986961 4.94101 0.026824 0.001509 0.998491
Localization: EC vs. CEC 0.400283 0.987351 4.79143 0.029219 0.929113 0.070887
Neural Networks: n=407;
Baseline Error=0.000;
Area under ROC Curve=1.000;
Correct Classification Rate=100%
Rank Sensitivity
Healthy Cells/Cancer Cells
Phase Transition Early---Invasive Cancer
Phase Transition N0---N12
Erythrocytes/Cancer Cells
Thrombocytes/Cancer Cells
Stick Neutrophils/Cancer Cells
Lymphocytes/Cancer Cells
Segmented Neutrophils/Cancer Cells
Eosinophils/Cancer Cells
Leucocytes/Cancer Cells
Monocytes/Cancer Cells
1
2
3
4
5
6
7
8
9
10
11
28794
20554
16562
8666
7464
7425
5836
5771
4024
3734
3230
Significant Factors Rank Kendal Tau-A P
Tumor Size 1 -0.316 0.000
Healthy Cells/Cancer Cells 2 0.315 0.000
T1-4 3 -0.307 0.000
Erythrocytes/Cancer Cells 4 0.307 0.000
Leucocytes/Cancer Cells 5 0.298 0.000
Thrombocytes/Cancer Cells 6 0.293 0.000
Lymphocytes/Cancer Cells 7 0.289 0.000
Segmented Neutrophils/Cancer Cells 8 0.280 0.000
Residual Nitrogen 9 -0.277 0.000
Phase Transition N0---N12 10 -0.248 0.000
Monocytes/Cancer Cells 11 0.240 0.000
Hemorrhage Time 12 -0.233 0.000
Phase Transition Early---Invasive Cancer 13 -0.225 0.000
Esophageal---Cardioesophageal Cancer 14 -0.194 0.000
Procedure Type 15 -0.192 0.000
Eosinophils/Cancer Cells 16 0.163 0.000
Chlorides 17 0.163 0.000
G1-3 18 -0.140 0.000
Tumor Growth 19 -0.117 0.001
Stick Neutrophils/Cancer Cells 20 0.105 0.01
Erythrocytes 21 0.103 0.01
Weight 22 0.100 0.01
Combined Procedure 23 0.098 0.01