kshivets o. local advanced lung cancer surgery

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LOCAL ADVANCED LUNG CANCER: OPTIMAL SURGERY STRATEGIES

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  • LOCAL ADVANCED LUNG CANCER: OPTIMAL SURGERY STRATEGIES Oleg Kshivets, MD, PhD Klaipeda University Hospital, Klaipeda, Lithuania 13 th World Conference on Lung Cancer July 31-August 4.2009, San Francisco, CA, the USA
  • Abstract:
    • LOCAL ADVANCED LUNG CANCER: OPTIMAL SURGERY STRATEGIES
    • Oleg Kshivets
    • Klaipeda University Hospital, Klaipeda, Lithuania
    • Objective: Survival of patients with local advanced non-small lung cancer (ALC) takes several months. Radical operations are complex and remain the prerogative of world best surgeons. The search of optimal surgery strategies for ALC patients (ALCP) with stage T3-4N0-2M0 was realized. We examined factors associated with generalization of ALC after complete (R0) combined pneumonectomies and lobectomies (PL).
    • Methods: We analyzed data of 155 consecutive ALCP (age=58.58.2 years; tumor diameter: D=6.72.6 cm) radically operated and monitored in 1985-2008 (m=143, f=12; pneumonectomy=88, bi/lobectomy=67, mediastinal lymphadenectomy=155; combined procedures with resection of pericardium=48, atrium=6, aorta=4, v. cava superior=9, carina=19, trachea=11, diaphragm=16, ribs=41, liver=7, esophagus=6; only surgery: S=66, adjuvant chemoimmunoradiotherapy-AT: CAV/gemzar+thymalin/taktivin+radiotherapy=52, postoperative radiotherapy=37; squamous=113, adenocarcinoma=30, large cell=12; T3=114, T4=41; N0=75, N1=35, N2=45; G1=35, G2=42, G3=78; stage IIB=60, IIIA=54, IIIB=41). Variables selected for 5-year survival (5YS) study were input levels of blood, biochemic and hemostatic factors, sex, age, TNMG, D. Survival curves were estimated by Kaplan-Meier method. Differences in curves between groups were evaluated using a log-rank test. Neural networks computing, Cox regression, clustering, discriminant analysis, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity.
    • Results: Cumulative 5YS was 58.3%, 10-years survival 49.7%. 91 ALCP were alive, 70 ALCP lived more than 5 years without any features of ALC progressing (life span: LS=2438.31004.2 days). 60 LCP died because of generalization during the first 5 years after radical procedures (LS=462.0367.8 days). AT significantly improved 5YS compared with S (P=0.003 by log-rank test) and with RT (P=0.002). Cox modeling displayed that 5YS of ALCP after PL significantly depended on: N0-2, T3-4, sex, AT, prothrombin index, fibrinogen-B, heparin tolerance, thrombocytes, cell ratio factors (P=0.000-0.047). Neural networks computing, genetic algorithm selection
    • and bootstrap simulation revealed relationships between 5YS and N0-2 (rank=1), AT (2), histology (3), type of operations (4), G (5), RT (6), heparin tolerance (7), S (8), T (9), sex (10), recalcification time (11), fibrinogen-B (12), eosinophils (13), protein (14), Hb (15), lymphocytes (16), prothrombin index (17), ESS (18), thrombotest (19), monocytes (20), thrombocytes/Cancer Cells (21), segmented neutrophils (22), coagulation time (23), eosinophils/Cancer Cells (24), D (25). Correct prediction of 5YS after PL was 100% by neural networks computing (area under ROC curve=1.0; error=0.0021).
    • Conclusions: Optimal surgery strategies for ALCP are: 1) availability of experienced surgeons because of complexity of radical procedures; 2) aggressive en block surgery and adequate mediastinal lymphadenectomy for completeness; 3) precise prediction; 4) adjuvant chemoimmunoradiotherapy for ALCP with unfavorable prognosis.
  • Data
    • Males 1 43
    • Females . 12
    • Age=5 8 . 5 8 . 2 years
    • Tumor Size=6. 7 2 . 6 cm
    • Only S urgery. .. ... ..... 66
    • Ad . Chemoimmuno radiotherapy therapy .. 52
    • Postoperative Radiotherapy 37
  • Adjuvant Therapy after Combined Procedures
    • Adjuvant Chemoimmunoradiotherapy (n=52): 1 cycle of bolus chemotherapy (CAVT) was initiated 10-14 days after resections and consisted of Cyclophosphamid 500 mg/m 2 IV on day 1, Doxorubicin 50 mg/m 2 IV on day 1, Vincristin 1.4 mg/m 2 IV on day 1. Immunotherapy consisted Thymalin or Taktivin 20 mg IM on days 1, 2, 3, 4 and 5. Chest radiotherapy (45-50 Gy) was administered since 7 day after 1 cycle chemoimmunotherapy at a daily dose of 1.8-2 Gy. No prophylactic cranial irradiation was used. From 2 to 3 weeks after completion of radiotherapy 3-4 courses of CAVT were repeated every 21-28 day. Since 1999 chemotherapy by gemzar 1250 mg/m 2 IV on day 1, 8, 15 and cisplatin 75 mg/m 2 on day 1 was initiated on 14 day after surgery and was repeated every 14 day (5-6 courses).
    • P/o Radiotherapy (n=37): Radiotherapy ( 60 CO; ROKUS, Russia) with a total tumor dose 45-50 Gy (2-4 weeks after surgery) consisted of single daily fractions of 180-200 cGy 5 days weekly. The treatment volume included the ipsilateral hilus, the supraclavicular fossa and the mediastinum from the incisura jugularis to 5-7 cm below the carina. The lower mediastinum was included in cases of primary tumors in the lower lobes. The resected tumor bed was included in all patients. Parallel-opposed AP-PA fields were used. All fields were checked using the treatment planning program COSPO. Doses were specified at middepth for parallel-opposed technique or at the intersection of central axes for oblique technique. No prophylactic cranial irradiation was used.
  • Combined Radical Procedures
    • Combined Pneumonectomy..... 88
    • Combined Bi/Lobectomy... 67
    • Combined Procedures with Resection of Pericardium... 48
    • Diaphragm..... 16
    • Atrium.................. 6
    • Vena Cava Superior.......... 9
    • Aorta......... 4
    • Carina................ 19
    • Trachea.. 11
    • Liver ..... 7
    • Esophagus... 6
    • Ribs................ 41
    • Mediastinal Lymphadenectomy.... 155
  • Staging
    • T3 114 N0.... 75 G1.. 35
    • T4.. 41 N1 35 G2.. 42
    • N2 45 G3.. 78
    • Central.. 83
    • Peripherical......................................... 72
    • Right...... 86
    • Left. 69
    • Adenocarcinoma.... 30
    • Squamous Cell Carcinoma.... 113
    • Large Cell Carcinoma....... 12
  • Survival Rate
    • 5-Year Survivors... 70 (45.2%)
    • Losses. 60 (38.7%)
    • General Life Span= 1384.9 1201.6 days
    • For 5-Year Survivors= 2438.31004.2 days
    • For Losses= 462.0367.8 days
    • Cumulative 5-Year Survival. 58.3%
    • Cumulative 10-Year Survival.......... 49.7%
  • General Local Advanced Lung Cancer Patients Survival after Complete Combined Procedures (Kaplan-Meier) ( n=15 5)
  • Results of Univariate Analysis in Prediction of Local Advanced Lung Cancer Patients Survival ( n=15 5)
  • Results of Cox Regression Modeling in Prediction of Local Advanced Lung Cancer Patients Survival after Complete Combined Procedures (n=155 ) Overall Chi2=89.907; df=15; P=0.000;
    • Factors Wald df P
    • N0-2 17 . 370 2 0.0 00
    • T3-4 8 . 512 1 0.00 4
    • Ad.Chemoimmunoradiotherapy 1 1 . 543 1 0.00 1
    • Gender 8 . 516 1 0.00 4
    • Prothrombin Index 6 . 577 1 0.0 10
    • Fibrinogen-B 8 . 832 1 0.00 3
    • Heparin Tolerance 6 . 064 1 0.01 4
    • T hrombocytes 5 . 241 1 0.0 22
    • Seg.Neutrophils/Cancer Cells 3 . 875 1 0. 047
    • Lymphocytes/Cancer Cells 5 .4 23 1 0. 020
  • Results of Discriminant Analysis in Prediction of Local Advanced Lung Cancer Patients Survival after Complete Combined Procedures (n=155)
    • Discriminant Function Analysis Summary
    • Wilks' Lambda: 0. 492 approx. F ( 22 , 107 )= 5 . 024 p< 0.0000 ; Correct Classification Rate=83.1%
    • Wilks' -Lambda P
    • Prothrombin Index 0.560 0.000
    • Fibrinogen-B 0 . 534 0.00 3
    • Recalcification Time 0. 524 0.0 09
    • N0-2 0 . 517 0.0 21
    • Heparin Tolerance 0 . 517 0.0 21
    • Monocytes/Cancer Cells 0. 517 0.0 21
    • Segmented Neutrophils/Cancer Cells 0. 516 0. 023
    • Stab Neutrophilc/Cancer Cells 0. 516 0. 024
    • Leucocytes/Cancer Cells 0. 516 0. 024
    • Eosinophils/Cancer Cells 0. 516 0. 0 2 5
    • Lymphocytes/Cancer Cells 0 . 516 0. 025
    • Monocytes (%) 0.515 0.027
    • Erythrocytes (tot) 0.513 0.033
    • Segmented Neutrophils (%) 0.513 0.034
    • T3-4 0.512 0.037
    • Lymphocytes (%) 0.512 0.037
    • Eosinophils (%) 0.512 0.037
    • Stab Neutrophils (%) 0.512 0.038
  • Results of Multi-Factor Clustering of Clinicopathological Data in Prediction of Local Advanced Lung Cancer Patients Survival after Complete Combined Procedures (n=155)
  • Results of Clustering in Prediction of Local Advanced Lung Cancer Patients Survival after Complete Combined Procedures (n=155)
    • Logic al Formulas based on Simple Mean
    • 5-Year Survivors :
    • 50.00