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2009

LOCAL ADVANCED ESOPHAGEAL AND CARDIOESOPHAGEAL CANCER: OPTIMAL TREATMENT STRATEGIESOleg Kshivets, Klaipeda University Hospital, Lithuania

Poster P-0205

OBJECTIVE: The survival of patients with local advanced of esophageal and cardioesophageal cancer (AEC) takes several months. Radical operations are extremely complex and remain the prerogative of several best surgeons of the world.The search of optimal treatment plan for AEC patients (AECP) with stage T2-4N1M1a was realized. We examined factors associated with the generalization of AECP after complete combined en block (R0) esophagectomies/esophagogastrectomies (E) through left or right thoracoabdominal incision.

METHODS: We analyzed data of 101 consecutive AECP (age=55.2 8.7 years; tumor size=6.9 2.9 cm) radically operated and monitored in 1975-2008 (males=81, females=20; E Ivor-Lewis=45, E Garlock=56; combined E with resection of 1-4 adjacent tissues of diaphragm=53, pericardium=32, lung=12, liver=12, splenectomies=22, left hemipancreatectomies=20, VCS=1, colon transversum=1; lymphadenectomy D2=45, D3=56; adenocarcinoma=62, squamos=37, mix=2; T2=30, T3=37, T4=34; N0=39, N1=13, M1a=49; M1b=0; G1=32, G2=19, G3=50; stage IIA=28, IIB=6, III=18, stage IVA=49; only surgery-S=60, adjuvant chemoimmunoradiotherapy-AT=41: 5-FU + thymalin/taktivin + radiotherapy 45-50Gy). Variables selected for 5-year survival (5YS) study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of AECP were evaluated using a log-rank test. Multivariate Cox modeling, multi-factor clustering, discriminant analysis, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing were used to determine any significant dependence.

RESULTS: General cumulative 5YS was 28.7%, 10-year survival – 21.3%, 20-year survival –17%. 29 AECP (28.7%) lived more than 5 years and 11 ECP - 10 years without any features of AEC progressing. 72 AECP (71.3%) died because of EC during first 5 years after surgery. AT significantly improved AECP 5YS after E (P=0.000 by log-rank test). Cox modeling displayed that 5YS of AECP after complete combined E significantly depended on: T, N, histology, stage, combined procedures, AT, weight, bilirubin, residual nitrogen, blood cell subpopulations, cell ratio factors (P=0.000-0.044). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS of AECP and sex (rank=1), AT (2), N (3), histology (4), type of combined procedure (5), T (6), tumor growth (7), G (8), lymphocytes (9), segmented neutrophils (10), ESS (11), leucocytes (12). Correct prediction of AECP survival after radical procedures was 100% by neural networks computing (area under ROC curve=1.0; error=0.0007).

Survival FunctionSurvival of AEPC after Complete Esophagogastrectomies, n=101

Real 5-Year Survival=28.7%; Real 10-Year Survival=21.3%Complete Censored

-5 0 5 10 15 20 25

Years after Complete Esophagogastrectomies

0.0

0.1

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0.4

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0.6

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0.9

1.0

1.1

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Variables in the EquationWald df P

Adjuvant ChemoimmunoradiotherapyCombined ProceduresTNHistologyTumor SizeStageErythrocytes/Cancer CellsHealthy Cells/Cancer CellsLeucocytes (abs)Stab Neutrophils (%)Segmented Neutrophils (%)Lymphocytes (%)Monocytes (%)Rest NitrogenBilirubinEosinophils (abs)Stab Neutrophils (abs)Lymphocytes (abs)WeightLeucocytes (tot)Eosinophils (tot)Segmented Neutrophils (tot)Lymphocytes (tot)

21.56929.34120.52714.6379.1076.01021.5034.0464.1674.32010.92919.32017.03915.2447.63719.36612.5214.4884.3144.4375.8686.2885.2105.952

153221311111111111111111

0.0000.0000.0000.0010.0110.0140.0000.0440.0410.0380.0010.0000.0000.0000.0060.0000.0000.0340.0380.0350.0150.0120.0220.015

Table 1. Results of multivariate proportional hazard Cox regression modeling in prediction of AECP survival after esophagogastrectomies (n=101)

Neural networks: 4-layer perceptron

NN Factors Sample n=101

Rank Error Ratio

123456789101112

SexAdjuvant ChemoimmunoradiotherapyNHistologyType of Combined ProceduresTTumor GrowthGLymphocytesSegmented NeutrophilsESSLeucocytes

123456789101112

0.3450.3330.2930.2530.2040.1940.1820.1640.0960.0390.0320.017

487.211470.496413.758356.585287.574273.031257.450231.768135.16755.61344.69624.230

Baseline ErrorArea under ROC CurveCorrect Classification Rate (%)

0.00071.000100.00

Table 2. Results of neural networks computing in prediction of 5-year survival of AECP after esophagogastrectomies (n=101: 29 5-year survivors and 72 losses).

AECP, n=101Number of

Samples=3333Significant Factors Rank Kendall’Tau-A P<

NStageTAdjuvant ChemoimmunoradiotherapyTumor SizeLymphocytes/Cancer CellsErythrocytes/Cancer CellsHealthy Cells/Cancer Cells

12345678

-0.195-0.192-0.1700.165-0.1530.1370.1370.136

0.010.010.010.050.050.050.050.05

Table 3. Results of bootstrap simulation in prediction of 5-year survival of AECP after esophagogastrectomies (n=101: 29 5-year survivors and 72 losses).

CONCLUSIONS: Optimal treatment strategies for AECP are: 1) availability of very experienced surgeons because of complexity radical procedures; 2) aggressive en block surgery and adequate lymphadenectomy for completeness; 3) precise prediction; 4) AT for AECP with unfavorable prognosis.

Model: lymphocytes-cancer cells-5YS