PRECISE PREDICTION OF 5-YEAR SURVIVAL OF ESOPHAGEAL AND CARDIOESOPHAGEAL CANCER PATIENTS AFTER ESOPHAGOGASTRECTOMIES

1. PRECISE PREDICTION OF
5-YEAR SURVIVAL OF ESOPHAGEAL AND
CARDIOESOPHAGEAL CANCER PATIENTS
AFTER ESOPHAGOGASTRECTOMIES
Oleg Kshivets , MD, PhD

2. Abstract: PRECISE PREDICTION OF 5-YEAR SURVIVAL OF ESOPHAGEAL AND
CARDIOESOPHAGEAL CANCER PATIENTS AFTER ESOPHAGOGASTRECTOMIES
Oleg Kshivets
OBJECTIVE: We examined factors in terms of precise prediction of 5-year survival (5YS) of esophageal and
cardioesophageal cancer (ECEC) patients (ECECP) (T1-4N0M1A) after complete (R0) esophagogastrectomies
(EG).
METHODS: We analyzed data of 407 consecutive ECECP (age=55.6±8.6 years; tumor size=6.7±3.3 cm)
radically operated and monitored in 1975-2011 (m=305, f=102;EG Garlock=271, EG Lewis=136, combined EG
with resection of pancreas, liver, diaphragm, colon transversum, lung, trachea, pericardium, splenectomy=125;
adenocarcinoma=212, squamous=185, mix=10; T1=62, T2=96, T3=140, T4=109; N0=167, N1=56, M1A=184,
G1=116, G2=96, G3=195; early ECEC=43, invasive=364). 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 1612.6±2070.5 days and cumulative 5-year survival (5YS) reached 40%,
10 years – 32.7%, 20 years – 23.5%. 101 ECECP lived more than 5 years without cancer. 215 ECECP died
because of ECEC. Cox modeling displayed (Chi2=232, df=26, P=0.000) that 5YS of ECECP significantly
depended on: phase transition (PT) N0—N1-M1A in terms of synergetics, cell ratio factors (CRF) (ratio between
cancer cells and blood cells subpopulations), T, G, tumor growth, tumor size, sex, age, adjuvant chemotherapy,
localization, blood cells, prothrombin index, ESS, blood chlorides, residual nitrogen (P=0.000-0.043). Neural
networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT N0--
N1-M1A (rank=1), PT early-invasive ECEC (rank=2), tumor size, prothrombin index, blood cells, ESS, age,
CRF, blood chlorides, residual nitrogen, localization, adjuvant chemotherapy. Correct prediction of 5YS was
100% by neural networks computing.
CONCLUSIONS: 5YS of ECECP after radical procedures significantly depended on: 1) PT ―early-invasive
cancer‖; 2) PT N0--N1-M1A; 3) CRF; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7)
anthropometric data; 8) adjuvant chemotherapy; 9) tumor localization.

3. Data:
• Males………………………………………………….305
• Females………..………………………………….......102
• Age=55.6±8.6 years
• Tumor Size=6.7±3.3 cm
• Only Surgery.………………………………………...324
• Adjuvant Chemoimmunoradio/Chemoimmunotherapy
(5FU+thymalin/taktivin, 5-6 cycles+RT 45-50Gy)…..83

4. Radical Procedures:
• Left Thoracoabdominal Esophagogastrectomies
(Garlock)……………………..………………271
• Right Thoracoabdominal Esophagogastrectomies
• (Ivor Lewis)………………….………………136
• Combined Esophagogastrectomies with
• Resection of Diaphragm, Pericardium, Lung,
Liver, Pancreas, etc…………..…………..…125
• 2-Field Lymphadenectomy….………………301
• 3-Field Lymphadenectomy….………………106

5. Left Thoracoabdominal Esophagogastrectomy
(Garlock)…………………………………….271

6. Garlock Procedures…………………..…271

7. Right Thoracoabdominal Esophagogastrectomy
(Ivor Lewis)......................................................136

8. Ivor Lewis Procedures…………………136

9. One-Stage Esophagogastroplasty
Intrapleural Anastomosis……….301
Neck Anastomosis……………….106

10. Staging:
• T1……62 N0..…167 G1…………116
• T2……96 N1……56 G2…………..96
• T3…..140 M1A..184 G3…………195
• T4…..109 M1B…..0
• Stage I…………..43 Stage IIA………...98
• Stage IIB………..28 Stage III…………54
• Stage IVA……..184 Stage IVB…………0
• Adenocarcinoma………..................................212
• Squamos Cell Carcinoma……………………185
• Mix Carcinoma..……………………………….10
• Early Cancer……43 Invasive Cancer…….364

11. Survival Rate:
• Alive………………………………………....167 (41%)
• 5-Year Survivors…………..……………….101 (24.8%)
• 10-Year Survivors…………………………...53 (13%)
• Losses………………………………………215 (52.8%)
• General Life Span=1612.6 2070.5 days
• For 5-Year Survivors=4404.4 2543.9 days
• For 10-Year Survivors=6095.9 2468.3 days
• For Losses=691.1 389.5 days
• Cumulative 5-Year Survival………………..40%
• Cumulative 10-Year Survival………………32.7%

12. General Esophageal/Cardioesophageal Cancer Patients Survival
after Complete Esophagogastrectomies (Kaplan-Meier) (n=407)
Surv iv al Function
Ge ne ral Esophage al and Cardioe sophage al Cance r Patie nts Surv iv al afte r
Comple te Esophagogastre ctomie s, n=407
Cumulativ e 5-Ye ar Surv iv al=40%; 10-Ye ar surv iv al=32.7%
Complete Censored
1.2
Cumulative Proportion Surviving
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
-5 0 5 10 15 20 25 30 35 40
Ye ars afte r Esophagogastre ctomie s

13. Results of Univariate Analysis of Phase Transition Early—Invasive
Cancer in Prediction of Esophageal/Cardioesophageal Cancer
Patients Survival (n=407)
Cumulativ e Proportion Surv iv ing (Kaplan-M e ie r)
Cumulativ e 5-Ye ar Surv iv al of Early Cance r Patie nts=100%
Cumulativ e 5-Ye ar Surv iv al of Inv asiv e Cance r Patie nts=33.2%
P=0.000 by Log-Rank Te st
Complete Censored
1.0
Cumulative Proportion Surviving
0.8
0.6
Invasive Cancer Patients=364
0.4
Early Cancer Patients=43
0.2
0.0
-0.2
0 5 10 15 20 25 30 35 40
Ye ars afte r Esophagogastre ctomie s

14. Results of Univariate Analysis of Phase Transition N0—N1M1A in
Prediction of Esophageal/Cardioesophageal Cancer Patients
Survival (n=407)
Cumulativ e Proportion Surv iv ing (Kaplan-M e ie r)
Cumulativ e 5-Ye ar Surv iv al of Cance r Patie nts with N0=60.3%
Cumulativ e 5-Ye ar Surv iv al of Cance r Patie nts with N1-M 1A=25.1%
P=0.000 by Log-Rank Te st
Complete Censored
1.0
Cumulative Proportion Surviving
0.9
0.8
Cance r Patie nts with N0=167
Cance r Patie nts with N1-M 1A=240
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 5 10 15 20 25 30 35 40
Ye ars afte r Esophagogastre ctomie s

15. Results of Univariate Analysis of Adjuvant Therapy in Prediction of
Esophageal/Cardioesophageal Cancer Patients Survival (n=407)
Cumulative Proportion Surviving (Kaplan-Meier)
Complete Censored
5-Year Survival after Adjuvant Treatment=60.8%;
5-Year Survival after Surgery Along=36.4%;
P=0.00018 by Log-Rank Test
1.0
0.9
Cumulative Proportion Surviving
0.8
Adjuvant Treatment, n=83
0.7
Only Surgery, n=324
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies

16. Results of Univariate Analysis of Tumor Localization in Prediction of
Esophageal/Cardioesophageal Cancer Patients Survival (n=407)
Cumulative Proportion Surviving (Kaplan-Meier)
Complete Censored
5-Year Survival of Esophageal Cancer Patients=49.1%;
5-Year Survival of Cardioesophageal Cancer Patients=34.4%;
P=0.003 by Log-Rank Test
1.0
0.9
Cumulative Proportion Surviving
0.8
0.7
Cardioesophageal Cancer Patients, n=272
0.6
Esophageal Cancer Patients, n=135
0.5
0.4
0.3
0.2
0.1
0.0
0 5 10 15 20 25 30 35 40
Years after Esophagogastrectomies

17. Results of Cox Regression Modeling in Prediction of
Esophageal/Cardioesophageal Cancer Patients Survival after Complete
Esophagogastrectomies (n=407)

18. Results of Neural Networks Computing in Prediction of
Esophageal/Cardioesophageal Cancer Patients Survival after Complete
Esophagogastrectomies (n=316)

19. Results of Bootstrap Simulation in Prediction of Esophageal Cancer
Patients Survival after Complete Esophagectomies (n=316)

20. Holling-Tenner Models of Esophageal /Cardioesophageal Cancer
Cell Population and Cytotoxic Cell Population Dynamics
P=0.000
z=a+bx+cx^(1.5)+dx^2+ex^(2.5)+fx^3+gy^(0.5)lny+hy^(0.5)+ie^(-y)
r^2=0.22525238 DF Adj r^2=0.20246569 FitStdErr=0.41643509 Fstat=11.157259
a=-324.15986 b=995.38663 c=-1201.3125 d=607.59325 e=-144.67162
f=13.358387 g=-1.246218 h=5.1686977 i=3.3595194
1
0.9 1
0.8 0.9
5-Year Survival
0.7 0.8
5-Year Survival
0.6 0.7
0.5 0.6
0.4 0.5
0.3 0.4
0.2 0.3
0.1 0.2
0 0.1
L ym 10
pho 0
cyt 7.5 7 8
es/ 5 6
Can .5 5
cer 2 0 3 4
Glucos
e
Ce
lls
P=0.000
z=a+blnx+c(lnx)^2+d(lnx)^3+e(lnx)^4+f(lnx)^5+glny+h(lny)^2+i(lny)^3+j(lny)^4+k(lny)^5
r^2=0.16790831 DF Adj r^2=0.13779973 FitStdErr=0.4329842 Fstat=6.1546145
a=-384.21482 b=1274.4403 c=-1669.3899 d=1080.7312 e=-345.52251 f=43.62225
g=0.5669461 h=-0.099389185 i=-0.2903548 j=-0.10570297 k=-0.011258385
1
0.9 1
0.8 0.9
5-Year Survival
0.7 0.8
5-Year Survival
0.6 0.7
0.5 0.6
0.4 0.5
0.3 0.4
0.2 0.3
0.1 0.2
0 0.1
Mo .5
noc 2 2 0
yte 8
s/C 1.5 1 6 7
anc 5
er C 0.5 0 3 4
Glucos
e
ells

21. Results of Kohonen Self-Organizing Neural Networks Computing in
Prediction of Esophageal/Cardioesophageal Cancer Patients
Survival after Complete Esophagogastrectomies (n=316)

22. Esophageal/Cardioesophageal Cancer Dynamics

23. Prognostic SEPATH-Model of Esophageal/Cardioesophageal
Cancer Patients Survival after Complete Esophagectomies, n=316

24. Conclusions:
• 5-Year Survival of Esophageal and Cardioesophageal Cancer
Patients after Radical Procedures Significantly Depended on:
• 1) Phase Transition “Early—Invasive Cancer”;
• 2) Phase Transition N0—N1M1A;
• 3) Cell Ratio Factors (ratio between cancer cells and blood cells
subpopulations);
• 4) Blood Cell Circuit;
• 5) Biochemical Homeostasis;
• 6) Hemostasis System;
• 7) Anthropometry;
• 8) Adjuvant Treatment;
• 9) Tumor Localization and Characteristics.

25. Address:
Oleg Kshivets
M.D., Ph.D.,
Consultant Thoracic,
Abdominal, General Surgeon
& Surgical Oncologist
• e-mail: okshivets@yahoo.com
• skype: okshivets
• http: //www.ctsnet.org/home/okshivets