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Z. Mihaylova



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-033 - The impact of plasma levels of Vascular Endothelial Growth Factor receptor 2(VEGF R2) and Hepatocyte Growth Factor (HGF) on survival in long-term survivors with advanced lung cancer (ALCP) (ID 2398)

      09:30 - 09:30  |  Author(s): Z. Mihaylova

      • Abstract

      Background
      Background HGF, a ligand of the c-met proto-oncogene, exhibits activating effects on human lung cancer both in vitro and in vivo (Hosoda H, 2012). The major mediator of angiogenic and permeability-enhancing effects of VEGF-A is the tyrosine kinase receptor VEGFR2.(Ferrara N. 2001, Takahashi H 2005). Some data indicate negative impact on survival of HGF and VEGF/VEGFR2 in lung cancer patients (Yang F, 2011;Kumara 2009, Han Y,2011 Ikeda N, 2010). EGFR-mutated lung cancer patients have longer survival under treatment with anti-EGFR TKI than non-mutated tumors. The biological reasons for long-surviving advanced lung cancer patients (ALCP) with not EGFR mutated tumors are not described.

      Methods
      Methods The plasma samples of ALCP without EGFR-mutation who survived more than 20 months (mo) are taken for analyses from serum/plasma bank storage at -80C. The measurement of HGF and VEGFR2 are done according to the manufacturing instructions of eBioscience Instant ELISA test and Platinum ELISA eBioscience test. Statistical analysis is made by SPSS.9.0.

      Results
      Results 30 plasma samples from 13 ALCP taken before treatment and at response evaluation thereafter are analyzed in duplicate. ALCP, mean age 60.4(range 44-75) years, 10/3 man/woman, 7/6 smokers/nonsmokers, 3/7/3 squamous/adeno/small cell, 10/3- ECOG PS 0/1, 6/7 died/censored, have mean PFS (measured from diagnosis till first progression) of 24.07 months (SD 5.2) and mean OS of 37.5 mo (SD 4.7). ALCP have disease confined to the thorax (pulmonary mets, pl. effusion) with 5 pts with bone and 2 with suprarenal mets. IHC confirmation of diagnosis is done in 60% of pts. The first line chemotherapy is platinum based with addition of VP-16 for small cell, Gemcitabine for squamous and Pemetrexed for adeno-histotype. Ten pts receive maintenance treatment and 9 had more than three lines of treatment. None of pts receive anti-angiogenesis therapy. The mean baseline values (13 samples) of VEGFR2 and HGF are 520,4 pg/ml(SD262,2) and 104,4 pg/ml(SD91,5), while at second (10 samples) and third (7samples) measurements mean values are 544,9 pg/ml (SD 95,5) / 49,2 pg/ml (SD 20,4) and 563,65 pg/ml (SD 152,1)/ 147,13 pg/ml(SD53,6). Strong negative Pearson correlation between plVEGFR2 and Hb levels is found (p=0.007). No correlation between albumin, LDH, WBC , PLT and cytokine baseline levels are found. According to the median baseline value of VEGFR2, ALCP with values bellow 422.7 pg/ml have significantly longer PFS (34,6mo) and OS (47,1mo) than those with VEGFR2 values above 422,7 – PFS -11,8 mo and OS-26,2 mo. (p=0.023 and p=0.020, ANOVA test). Median baseline HGF values of 88.3 bellow/above separate ALCP with longer/shorter OS 46/32,1 mo but without reaching statistical significance (p=0.17)

      Conclusion
      Conclusions Classical clinical prognostic factors cannot identify ALCP with long survival –PS and numbers of therapeutic lines have positive effect on prognosis. Circulating baseline angiogenesis-related cytokines particularly VEGFR2 and HGF might be used for biological determinates of long survivors identification among patients with advanced lung cancer. However further studies with enlarged patients number with long survival are needed.