Cardioesophageal Cancer: Best Treatment Strategies

ABSTRACT

Objective: We examined the clinicomorphologic factors associated with the low- and high-risk of generalization of cardioesophageal cancer (CEC) (T1-4N0-2M0) after complete (R0) esophagogastrectomies (EG) through left thoracoabdominal incision.

Methods: We analyzed data of 175 consecutive CEC patients (CECP) (age = 55.3 ± 8.7 years; tumor size = 6.9 ± 3.3 cm) radically operated and monitored in 1975-2008 (males = 132, females = 43; combined EG with resection of pancreas, liver, diaphragm, colon transversum, lung, trachea, pericardium, splenectomy - 71; lymphadenectomy D2 - 98, D3-D4 - 77; esophagogastroanastomosis - 98, esophagoenteroanastomosis - 77; adenocarcinoma - 112, squamous cell carcinoma - 58, mix - 5; T1 - 24, T2 - 38, T3 - 66, T4 - 47; N0 - 70, N1 - 22, N2 - 83; G1 - 52, G2 - 34, G3 - 89; surgery alone - 128; surgery and adjuvant chemoimmunotherapy-AT: 5FU + thymalin/taktivin, 5-6 cycles - 47 CECP).

Variables selected for 5-year survival (5YS) study were input levels of 45 blood parameters, sex, age, TNMPG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of CECP were evaluated using a log-rank test. Multivariate Cox modeling, multi-factor clustering, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing were used to determine any significant dependence.

Results: For total of 175 CECP overall life span (LS) was 1381.6 ± 1486.7 days, (median - 723 days) and cumulative 5YS reached 36.1%, 10 years - 26.6%. 53 CECP lived more than 5 years without CEC progressing. 104 CECP died because of CEC during the first 5 years after surgery. 5YS of CECP was superior significantly after AT (69.9%) compared with surgery alone (26.6%) (P = 0.000 by log-rank test). Cox modeling displayed that 5YS of CECP (n = 175) after complete EG significantly depended on: phase transition (PT) early-invasive CEC, PT N0-N12, AT, age, T, tumor growth, Rh-factor, blood cell subpopulations, cell ratio factors (P = 0.000-0.047). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and early-invasive CEC (rank = 1), PT N0-N12 (rank = 2), AT (rank = 3), T (4), gender (5), prothrombin index (6), weight (7), glucose (8), age (9), coagulation time (10), eosinophils/ cancer cells (11), erythrocytes/cancer cells (12), hemorrhage time (13), protein (14), Hb (15), segmented neutrophils/ cancer cells (16), stab neutrophils/cancer cells (17). Correct prediction of 5YS was 100% by neural networks computing (error = 0.0009e-12; urea under ROC curve = 1.0).

Conclusions: Best treatment strategies for CECP are: 1) screening and early detection of CEC; 2) availability of very experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate abdominal, mediastinal, cervical lymphadenectomy for completeness; 4) high-precision prediction; 5) adjuvant chemoimmunotherapy for CECP with unfavorable prognosis.