Cardioesophageal and Esophageal Cancer: Optimization of ManagementOleg Kshivets, MD, PhD

Abstract: Oleg KshivetsCardioesophageal and Esophageal Cancer: Optimization of Management

OBJECTIVE:    Search of best treatment plan for cardioesophageal/esophageal cancer (CEC) patients (CECP) was realized.

METHODS: We analyzed data of 411 consecutive CECP (age=55.6±8.7 years; tumor size=6.7±3.3 cm) radically operated (R0) and monitored in 1975-2012 (m=307, f=104; esophagogastrectomy- EG Garlock=271, EG Lewis=140, combined EG with resection of pancreas, liver, diaphragm, colon transversum, lung, trachea, pericardium, splenectomy=127; adenocarcinoma=216, squamous=185, mix=10; T1=62, T2=99, T3=141, T4=109; N0=170, N1=57, M1A=184, G1=116, G2=98, G3=197; early CEC=43, invasive=368; esophageal cancer=139, cardioesophageal cancer=272): only surgery-S=327, adjuvant treatment-AT=84 (chemoimmunoradiotherapy=36: 5-FU+thymalin/taktivin +radiotherapy 45-50Gy, adjuvant chemoimmunotherapy=48). Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of CECP were evaluated using a log-rank test. Cox modeling, clustering, SEPATH, Monte Carlo, bootstrap simulation and neural networks computing were used to determine any significant dependence.    RESULTS: For total of 411 CECP overall life span (LS) was 1632.2±2141.6 days, (median=783 days) and cumulative 5-year survival (5YS) reached 40.1%, 10 years – 32.9%, 20 years – 24%. 102 CECP lived more than 5 years without CEC progressing. 216 CECP died because of CEC during the first 5 years after surgery. 5YS was superior significantly after AT (61.7%) compared with S (36.2%) (P=0.000 by log-rank test). Cox modeling displayed that 5YS significantly depended on: phase transition (PT) early-invasive CEC in term of synergetics, PT N0-N1M1A, AT, cell ratio factors (P=0.000-0.038). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive CEC (rank=1), PT N0-N1M1A (rank=2), AT (3), segmented neutrophils/cancer cells-CC) (4), lymphocytes/CC (5), monocytes/CC (6). Correct prediction of 5YS was 100% by neural networks computing.

    CONCLUSIONS: Optimal management strategies for CECP are: 1) screening and early detection; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymphadenectomy for completeness; 4) high-precision prediction; 5) adjuvant treatment for CECP with unfavorable prognosis.

Data: Males………………………………………………….307 Females………..………………………………….......104

Age=55.6±8.7 years Tumor Size=6.7±3.3 cm Only Surgery.………………………………………...327 Adjuvant Chemoimmunoradio/Chemoimmunotherapy

(5FU+thymalin/taktivin, 5-6 cycles+RT 45-50Gy)…..84

Radical Procedures: Left Thoracoabdominal Esophagogastrectomies

(Garlock)……………………..……………………..271 Right Thoracoabdominal Esophagogastrectomies (Ivor Lewis)………………….……………………...140 Combined Esophagogastrectomies with Resection of Diaphragm, Pericardium, Lung, Liver,

Pancreas, etc…………..…………..………………...127 2-Field Lymphadenectomy….……………………..303 3-Field Lymphadenectomy….……………………..108

Staging: T1……62 N0..…170 G1…………116 T2……99 N1……57 G2…………..98 T3…..141 N2…..184 G3…………197 T4…..109 M1……..0 Adenocarcinoma………..................................216 Squamos Cell Carcinoma……………………185 Mix Carcinoma..……………………………….10 Early Cancer……43 Invasive Cancer…….368

Survival Rate: Alive………………………………………....170 (41%) 5-Year Survivors…………..……………….102 (24.8%) 10-Year Survivors…………………………...54 (13%) Losses………………………………….……216 (52.6%) General Life Span=1632.2±2141.6 days For 5-Year Survivors=4491.3±2679.0 days For 10-Year Survivors=6228.6±2632.2 days For Losses=648.6±387.8 days Cumulative 5-Year Survival………………..40.1% Cumulative 10-Year Survival………………32.9%

General Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (Kaplan-Meier) (n=411)

Results of Univariate Analysis of Phase Transition Early—Invasive Cancer in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival (n=411)

Results of Univariate Analysis of Phase Transition N0—N1-2 in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival (n=411)

Results of Univariate Analysis of Adjuvant Therapy in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival (n=411)

Results of Univariate Analysis of Tumor Localization in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival (n=411)

Results of Univariate Analysis of Tumor Hystology in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival (n=411)

Results of Univariate Analysis of Tumor Growth in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival (n=411)

Results of Discriminant Fanction Analysis in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after

Surgery (n=318)

Results of Multi-Factor Clustering of Clinicopathological Data in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophagectomies (n=318)

Results of Cox Regression Modeling in Prediction of Esophageal/Cardioesophageal Cancer

Patients Survival after Surgery (n=411)

Results of Neural Networks Computing

in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=318)

Results of Bootstrap Simulation in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophagectomies (n=318)

Holling-Tenner Models of Esophageal/Cardioesophageal Cancer Cell Population and Cytotoxic Cell Population Dynamics

Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=318)

Esophageal/Cardioesophageal Cancer Dynamics

Results of Structurul Equation Modeling in Prediction of Esophageal/Cardioesophageal Cancer Patients Survival after

Esophagectomies, n=318

Conclusions: Optimal management strategies for esophageal and

cardioesophageal cancer patients are: 1) screening and early detection; 2) availability of experienced thoracoabdominal

surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node

dissection for completeness; 4) high-precision prediction; 5) adjuvant treatment for esophageal and

cardioesophageal cancer patients with unfavorable prognosis.

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