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Jacqueline Pierce



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    MA22 - New Therapeutics, Pathology, and Brain Metastases for Small Cell and Neuroendocrine Tumour (ID 925)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 206 BD
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      MA22.03 - SCLC Circulating Tumour Cell Derived Explants: The Clinical Characteristics of Patients Whose Samples Generate CDX (ID 12969)

      15:25 - 15:30  |  Author(s): Jacqueline Pierce

      • Abstract
      • Presentation
      • Slides

      Background

      Small cell lung cancer (SCLC) prognosis is dismal, with minimal improvement in recent years. Work with SCLC cell lines and targeted therapies have been disappointing when translated into clinical practice. Circulating tumour cells (CTCs) represent a readily accessible liquid biopsy, which can be used to generate CTC derived explants (CDXs) for the study of SCLC biology and the investigation of biomarkers and therapeutics. These clinically relevant models appear to mirror patient response to therapeutics. Our aim was to assess if the patients whose samples generated a CDX represent the SCLC population, and determine if the clinical features of these patients offer insight into CTC biology.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This was a single centre, retrospective analysis of 147 SCLC patients who had participated in The CHEMORES Study in which SCLC patients were asked to donate blood samples for the discovery and validation of novel biomarkers. Paired patient blood samples were taken for CTC enumeration using CellSearch Technology and for attempted CDX model generation. We obtained demographic and clinical information on these patients, and analysed the data for differences between patients whose blood samples generated a CDX and those whose did not.

      4c3880bb027f159e801041b1021e88e8 Result

      231 paired blood samples were taken from 147 patients, with 45 CDXs successfully generated from 34 patients. CTC number was significantly higher in samples which generated a CDX than those which didn’t, p=0.001. Successful progression samples had a significantly lower CTC number than successful baseline samples, p=0.026. There was no significant difference in age, gender, pack year history, performance status, stage, chemosensitivity or the presence of liver or brain metastases between patients whose samples did and did not generate a CDX. Metastatic burden was significantly higher in patients whose samples generated a CDX, p=<0.001. Progression free (PFS) and overall survival were significantly shorter in patients whose samples generated a CDX, p=<0.001

      8eea62084ca7e541d918e823422bd82e Conclusion

      CTC number correlates with CDX success, although a specific CTC phenotype may be more important. CTCs at progression may have a more aggressive phenotype than those at baseline. CDXs appeared to represent the SCLC population which is important when translating knowledge gained by studying CDXs into clinical practice. CTCs may play a role in the widespread metastatic dissemination of SCLC and thus survival of patients. Shortened PFS in the absence of difference in chemosensitivity may be due to outliers with particularly long PFS in the unsuccessful group. Further genomic and phenotypic analysis of subpopulations of CTCs may provide further insight.

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