Kshivets O. Lung Cancer Stage III Surgery

Click here to load reader

download Kshivets O. Lung Cancer Stage III Surgery

of 40

Embed Size (px)

description

PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS WITH STAGE III AFTER COMPLETE RESECTIONS

Transcript of Kshivets O. Lung Cancer Stage III Surgery

  • PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS WITH STAGE III AFTER COMPLETE RESECTIONS Oleg Kshivets, MD, PhD Department of Surgery, Siauliai Cancer Center, Siauliai, Lithuania 2004 ASCO Annual Meeting, New Orleans, Louisiana, the USA, June 3-8, 2004
  • Abstract
        • PREDICTION OF 5-YEAR SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS WITH STAGE III AFTER COMPLETE RESECTIONS
        • Oleg Kshivets
        • Surgery Department, Siauliai Cancer Center, Lithuania
    • OBJECTIVE: The influence of clinicomorphological data on 5-year survival (5YS) and life span (LS) of non-small lung cancer (LC) patients (LCP) with stage IIIA and IIIB after radical resections (R0) was investigated.
    • METHODS: In trial (1985-2003) the data of consecutive 139 LCP (age=57.80.6 years; male=129, female=10; tumor diameter: D=5.60.2 cm; pneumonectomy=75, upper lobectomy=40, lower lobectomy=17, middle lobectomy=1, bilobectomy=6, combined procedures with resection of pericardium, left atrium, aorta, v. cava superior, carina, diaphragm, ribs=67; only surgery=54, adjuvant chemoimmunoradiotherapy-AT=40: CAV/gemzar-cisplatin + thymalin/taktivin + radiotherapy=40, postoperative radiotherapy-PR=45) with stage III (squamous cell=94, adenocarcinoma=34, large cell=11; stage IIIA=109, stage IIIB=30; T1=11, T2=48, T3=50, T4=30; N0=13, N1=32, N2=94; G1=24, G2=31, G3=84) was reviewed. Variables selected for 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 and Monte Carlo simulation were used to determine any significant regularity.
    • RESULTS: General life span was 1019.3 82.9 days (median=519). 49 LCP (35.3%) were alive, 44 from them lived more than 5 years (31.7%) without any features of progressing. 87 LCP (62.6%) died because of relapses and generalization during the first 5 years after surgery. Cox modeling displayed that 5-year survival of LCP (n=139) after complete resections significantly depended on: N0-2 (P=0.027), histology (P=0.002), G1-3 (P=0.036), character of operation (P=0.010), AT (P=0.0003), 20 blood factors (P=0.001-0.044). Neural networks computing and genetic algorithm selection revealed relationships between 5-year survival of LCP and AT (rank=1), G1-3 (2), PR (3), N0-2 (4), tumor growth (5), histology (6), procedure type (7), stage IIIA/IIIB (8), percent of monocytes (9), ESS (10). Correct prediction of LCP survival after radical procedures was 75.6% by logistic regression (odds ratio=7.57), 85.5% by discriminant analysis and 100% by neural networks computing (area under ROC curve=1.0; error=0.0027).
  • Factors:
    • 1) Antropometric Factors... 4
    • 2) Blood Analysis... 26
    • 3) Hemostasis Factors. 8
    • 4) Cell Ratio Factors... 9
    • 5) Lung Cancer Characteristics. 8
    • 6) Biochemic Factors... 5
    • 7) Treatment Characteristics. 5
    • 8) Survival Data... 3
    • In All.68
  • Main Problem of Analysis of Alive Supersystems (e.g. Lung Cancer Patient Homeostasis): Phenomenon of Combinatorial Explosion
    • Number of Factors:..... 68
    • Number of Possible Combination for Random Search:.... n!=68!=2.5e+96
    • Operation Time of The 7G Superteracomputer (1000TFLOPS) (The 21 st Century). 7.9e+73 Years
    • Age of Universe.1.3e+13 Years
  • Basis:
    • NP RP P
    • n! n*n*2(e+n) or n log n n
    • AI CSA+S+B SM
  • Radical Procedures:
    • Pneumonectomy.. 75
    • Upper/Lower Bilobectomy... 6
    • Upper Lobectomy... 40
    • Lower Lobectomy... 17
    • Middle Lobectomy.... 1
    • In All...139
  • Combined & E xtensive R adical P rocedures with R esection of P ericardium, L eft A trium, A orta, V ena C ava S uperior, V ena A zygos, C arina, Trachea, D iaphragm, C hest W all , Ribs, etc... 67 Sistematic Mediastinal Lymph Node-N2 Dissection.. 139
  • Staging:
    • T1.11 N0....13 G1..24
    • T2.48 N132 G2..31
    • T3.50 N294 G3..84
    • T4.30 Stage IIIA...109 Stage IIIB...30
    • Squamous Cell Carcinoma...94
    • Adenocarcinoma34
    • Large Cell Carcinoma...11
  • Samplings:
    • Adjuvant Chemoimmunoradiotherapy .. 40
    • P/O Radiotherapy ..... 45
    • Surgery Alone .... 54
    • In All..139
    • Male...129
    • Female.....10
    • Age=57.80.6 years
  • Adjuvant Therapy after Complete Resections
    • Adjuvant Chemoimmunoradiotherapy: 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. 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: 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.
  • Survival Rate of Lung Cancer Patients with Stage III after Complete Resections (n=139):
    • Alive. 49 (35.3%)
    • 5-Year Survivors. 44 (31.7%)
    • Losses from Lung Cancer.. 87 (62.6%)
    • Life Span=1019.382.9 days
    • 5-Year Survivors with Stage IIIA. 38 (34.9%)
    • 5-Year Survivors with Stage IIIB... 6 (20%)
    • 5-Year Survivors after Surgery alone... 11(20.4%)
    • 5-Year Survivors after P/o Radiotherapy. 14(31.1%)
    • 5-Year Survivors after Adjuvant Chemoimmunoradiotherapy.. 18 (45%)
    • At All.139 (100%)
  • Significant Factors between Lung Cancer Losses & 5-Year Survivors with Stage III (n=131)
    • Factors MeanSD MeanSD
    • (Survivors) (Losses) P
    • n=44 n=87
    • Weight (kg) 72.312.3 66.812.2 0.016
    • Seg.Neutrophiles (%) 64.911.9 69.29.7 0.030
    • Monocytes (%) 5.52.8 4.32.8 0.021
    • Prothrombin Index (%) 94.86.9 99.08.2 0.004
    • Sul. Probe 1.950.17 1.860.19 0.009
    • Fibrinogen-B 1.160.37 1.440.87 0.046
    • Life Span (days) 2283.5684.6 424.9309.1 0.0000
    • Log-Rank Test P
    • N1 vs. N2 0.006
    • Ad.CHIRT 0.0005
    • Surgery Alone 0.015
  • Product-Limit (Kaplan-Maier) Analysis Results in Prediction of Lung Cancer Patients Survival with Stage III after Complete Resections (n=139) Graph of Survival Times vs. Cum. Proportion Surviving
  • Cumulative Proportion Lung Cancer Patients Surviving (Kaplan-Meier) (n=139)
  • Cumulative Proportion Lung Cancer Patients Surviving (Kaplan-Meier)
  • Results of Multivariate Proportional Hazard Cox Regression Analysis:
  • Results of Multifactor Analysis in Prediction of Lung Cancer Patients Survival with Stage IIIA & IIIB (n=139)
  • Results of Discriminant Analysis in Prediction of Lung Cancer Patients Survival with Stage III after Complete Resections (n=131)
    • Discriminant Function Analysis Summary
    • Wilks' Lambda: .57124 approx. F (17,113)=4.9890 p< 0.0000
    • Wilks' Partial F-remove
    • Lambda Lambda (1,113) P-level