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G. Doughton



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    MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
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      MA 11.02 - Circulating Tumour DNA in Early Stage NSCLC: High Sensitivity Analysis in Low Burden Disease. LUCID Study Update (ID 9598)

      11:00 - 12:30  |  Author(s): G. Doughton

      • Abstract
      • Presentation
      • Slides

      Background:
      To improve treatment selection and outcomes for patients with early stage non-small cell lung cancer (NSCLC) the development of an effective biomarker to diagnose and characterise the tumour and to detect residual disease after curative-intent treatment is crucial. Circulating tumour DNA (ctDNA) is a promising means to detect and track tumours non-invasively, as the genomic alterations in plasma are representative of the tumour’s clonal populations and their levels correlate with the burden of disease. Furthermore, ctDNA has shown promise for detecting minimal residual disease after treatment in several cancer types. This could help in the selection of patients that, after surgery or radical radiotherapy, will benefit from subsequent treatment. Nonetheless, more sensitive techniques are needed to enable the detection and study of ctDNA at very low concentrations in settings such as these.

      Method:
      The LUCID study (early stages of non-small cell LUng cancer - CIrculating tumour DNA) was designed to prospectively collect plasma samples from patients with early-stage NSCLC before and after treatment with surgery or radiotherapy (±chemotherapy), and during a minimum follow up of 3 years after diagnosis, in order to explore the clinical utility of ctDNA. For high sensitivity detection of ctDNA, TAilored Panel Sequencing (TAPAS) was developed: exome sequencing of tumour tissue enables the creation of patient-specific panels to analyse in parallel, large numbers of mutations with high sequencing depth. Plasma samples are being analysed using this approach to assess the levels of ctDNA at diagnosis and after radical treatment.

      Result:
      100 patients were recruited to the study. Longitudinal plasma sample collection and analysis are on-going. Preliminary analysis of the tumour tissue and pre-surgical plasma samples from 19 surgical patients show that most patients with early-stage NSCLC have detectable ctDNA. Analysis of additional samples will be presented.

      Conclusion:
      Preliminary data from LUCID suggest that the methods we have developed have high sensitivity and will allow detection of ctDNA at rates higher than previously reported. These methods will enable the study of ctDNA in early-stage cancers. We are also exploring the utility of these techniques for detection of minimal residual disease after radical treatment, as a potential tool to guide adjuvant or subsequent post-radiotherapy treatment.

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