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M. Ilouze



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    MINI 04 - Clinical Care of Lung Cancer (ID 102)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI04.09 - The Impact of Next-Generation Sequencing on Clinical Decisions in Lung Cancer (ID 2978)

      16:45 - 18:15  |  Author(s): M. Ilouze

      • Abstract
      • Presentation
      • Slides

      Background:
      In the last decade, important advances have been made in understanding genetic and molecular mechanisms of Non-Small Cell Lung Cancer (NSCLC) tumor development. This has led to the creation of innovative, targeted drugs that significantly prolong survival in advanced patients. Recent data shows that 63% of NSCLC tumors harbor at least one activating driver mutation, including treatable mutations such as RET, HER2 and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes that account for 23% of the patients. Clinical cancer genomic profiling tests based on Next Generation Sequencing (NGS) technologies are capable to reveal clinically actionable genetic alterations in up to three times the number of actionable alterations detected by current diagnostic tests. However, there is no data regarding the true impact of these tests on clinical decisions in lung cancer. In this study, our objective is to evaluate the impact of NGS-based genetic profiling tests on treatment strategy in NSCLC patients in the real life setting, considering the additional diagnostic tests performed. Based on clinical experience from Israel, NGS-based tests actively change treatment plans, but the effect size is unknown and merits further investigation.

      Methods:
      In this retrospective study, data is collected from patient files at the Thoracic Cancer Unit of Davidoff Cancer Center, Rabin Medical Center, Israel. The current study population is 78 NSCLC patients who performed NGS-based genetic profiling tests.

      Results:
      Out of 78 patients, 58 patient files have already been reviewed and 6 were excluded. Treatment decision change rate after NGS testing was 33% (17 out of 52 patients were treated with a targeted therapy - 24% of the current study population). Interestingly, 9 patients became EGFR and ALK positive by NGS after the previous standard local molecular testing was negative. Based on the RECIST criteria of response evaluation, 41% of the patients had a partial response after switching to targeted therapy, 23% had a complete response, 18% experienced progressive disease and 18% were not evaluated yet. Survival rates will be calculated further in the study based on data availability.

      Conclusion:
      The use of NGS for tumor classification and treatment planning holds a great potential for improving patient life quality and survival. In this study, we aimed to determine its clinical impact in the real life setting in the treatment of lung cancer. Our partial results show that in addition to performing standard molecular testing for NSCLC, almost a quarter of the patients can be identified having an actionable driver mutation and switched to targeted therapy. Most of these patients showed a positive response to treatment. Although this topic needs to be further assessed in large randomized controlled trials, these positive results emphasize the importance of upfront multiplex testing or suggest such technology as a reflex test in places where the primary kits are done first in sake of cost-benefit.

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    P2.06 - Poster Session/ Screening and Early Detection (ID 219)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P2.06-009 - Oral Glucose Tolerance Test as a Diagnostic Tool in Lung Cancer (ID 1040)

      09:30 - 17:00  |  Author(s): M. Ilouze

      • Abstract
      • Slides

      Background:
      Previous studies have demonstrated that volatile organic compounds (VOCs) in exhaled breath can distinguish between healthy and affected individuals, and can even discern between SCLC and NSCLC and within the subtypes of lung cancer (LC) and its mutations status. The current study assessed the differences in glucose metabolism on the volatile signature in LC through an oral glucose tolerance test (OGTT).

      Methods:
      This cohort included forty participants (22 control participants whom are at high risk for LC, 18 study participants whom have active, naïve lung cancer). Pre-OGTT and Post-OGTT blood glucose levels and exhaled breath samples were measured with a lay period of 90 minutes. A proton transfer reaction mass spectrometer (PTR MS) detected and measured the VOCs. The data was then analyzed using a series of feature selection methods to identify relevant inputs for multilayer perceptron (MLP) models to distinguish LC patients from controls, with and without the consideration of the glucose effect.

      Results:
      The feature selection method “infogain” revealed a combination of 14 masses (m/e) that were different between the two groups without considering the glucose effect. All the average values of these masses were higher in the LC group except for m/e 52, which was higher in the high-risk group. These 14 masses enable us to distinguish between the two groups with an average accuracy of 91.67% for three internal validation tests of a MLP (threshold set at 0.45). The analysis of the effect of glucose revealed that several m/e increased more for the control group whereas others increased more for the LC group. Moreover, three feature selections, each with a different combination of 4 masses, allowed the design of three MLPs that yielded 90% for K-fold cross-validation accuracy. Figure 1



      Conclusion:
      This study showed that breath analysis could discriminate between the high-risk and LC group. Furthermore, it demonstrated that glucose metabolism leaves a unique VOC pattern in the LC group. These findings may assist in the development of a non-invasive screening method for lung cancer.

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