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Milena Cavic



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    P1.03 - Biology (ID 161)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.03-07 - Advantages and Setbacks of EGFR Mutation Testing from Liquid Biopsy of Advanced Lung Adenocarcinoma Patients in Serbia (ID 1414)

      09:45 - 18:00  |  Author(s): Milena Cavic

      • Abstract
      • Slides

      Background

      With approximately 8000 newly diagnosed cases in 2018, lung cancer has become the most common malignant disease in Serbia. EGFR gene mutation testing as companion diagnostic for treatment with tyrosine kinase inhibitors (TKIs) has been introduced in 2011 in Serbia only for advanced lung adenocarcinoma patients. In 2016. additional EGFR mutation testing was employed from liquid biopsy samples of patients who have progressed on TKIs or whose biopsies were unavailable for initial testing.

      Method

      EGFR mutation testing was performed from FFPE tumor samples or glass slides of advanced lung adenocarcinoma patients (stage IIIB or IV, and ECOG performance status 0, 1 or 2,) using the Cobas® EGFR Mutation Test. Patients with sensitizing EGFR mutations were treated with first generation TKIs until progression. Resistance to TKI was tracked from liquid biopsy samples (10 mL of plasma) of patients who progressed in the first three months of first-line TKI treatment.

      Result

      In the period between 2011-2018, 4750 EGFR mutation analyses were performed, with around 11% of mutated samples detected, which is in good accordance with literature data for the Caucasian population. Although EGFR mutation testing has been successfully implemented in routine management of lung cancer patients in Serbia with an average turnaround time of 5 working days, we still had approximately 3% of tumor samples with insufficient material for successful DNA isolation. In such cases, 124 plasma samples were tested, and 9 mutations were detected (7.3 % of total) with a turnaroud time of 2 days, and a 99.2 % testing success rate. Testing liquid biopsy samples of 104 patients who progresses on first-line TKIs showed an accordance rate of 93 % with driver mutations, and 34 patients (33% of total) had the T790M mutation which rendered them eligible for third-generation TKIs in Serbia. Additional 2 patients who tested EGFR wt from plasma and were rebiopsied proved to have the T790M mutation as well.

      Conclusion

      In developing countries, testing from circulating tumor DNA, as an alternative sample source for patients with scarce biopsy material or without any at all is an acceptable cost/benefit option. However, routine monitoring of molecular disease progression from liquid biopsy before clinical progression occurs has still not been implemented in Serbia for economic reasons.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-50 - Low Temperature Plasma Needle Induces Cell Cycle Arrest of Epithelial Lung Cancer Cells in Vitro via a p21-Dependent Pathway (Now Available) (ID 780)

      10:15 - 18:15  |  Presenting Author(s): Milena Cavic

      • Abstract
      • Slides

      Background

      Low temperature plasma sources which operate at atmospheric pressure produce reactive oxygen species (ROS) and reactive nitrogen species which can cause cancer cell death. In this study we investigated the effect of our low temperature plasma needle system on a non-small cell lung cancer cell line A549 and studied its mechanism of action.

      Method

      The housing of the pen lookalike atmospheric plasma source (plasma needle) was made of Teflon. A Pyrex glass tube (o.d. 6 mm and i.d. 4 mm) through which 1 slm of helium was released as the feeding gas was positioned within the housing. The central electrode, a tungsten wire, was powered with a 13.56 MHz sine wave and placed within a ceramic tube inside the glass tube. The central electrode was sticking 1 mm outside of the ceramic and glass tubes, so the discharge occurred on its tip as a weak glow. The cytotoxic activity was determined using MTT assay. The potential of inducing cell cycle perturbations and apoptosis, and changes in the level of ROS was investigated by flow cytometry. The influence of plasma treatment on growth inhibition of multicellular tumor spheroids (MCTS) was also investigated. Evaluation of gene expression was performed by qPCR. All experiments were performed in triplicate, with statistical significance set at p<0.05.

      Result

      Our plasma needle exerted a cytotoxic effect with lower sensitivity towards BEAS-2B normal cells than towards A549 cells. A decrease in the number of cells in the G1 phase (up to 45%), increase in the G2 phase (up to 27%), and an increase in the sub-G1 phase (up to 12%) with fragmented DNA was detected upon treatment. The plasma treatment exerted a mild apoptotic effect (around 15% of apoptotic cells), and an increase in the level of ROS in a power dependent manner. There was no significant reduction in growth of MCTS after plasma treatment under investigated experimental conditions. A statistically non-significant proapoptotic effect (increase in Bax, decrease in Bcl2 and decrease in SKP2) was observed at the genetic level. A significant overexpression of the cyclin-dependent kinase inhibitor 1 (p21) was also observed at the genetic level in a power dependent manner.

      Conclusion

      Our low temperature plasma needle induced cell cycle arrest of epithelial lung cancer cells through overexpression of p21. The effect of combined plasma treatment with existing treatment modalities (cisplatin, PARP inhibitors) is currently under in vitro investigation.

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