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M.P. Davies

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    WS 01 - IASLC Supporting the Implementation of Quality Assured Global CT Screening Workshop (By Invitation Only) (ID 632)

    • Event: WCLC 2017
    • Type: Workshop
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      WS 01.24 - Designs of Possible Biomarkers for Future Screening Programs? (ID 10665)

      08:30 - 21:00  |  Author(s): M.P. Davies

      • Abstract
      • Slides

      The integration of biomarkers into lung cancer CT screening programmes remains an ‘unfulfilled promise’ in lung cancer research. There are two specific areas that biomarkers could contribute: (i) identification of high risk individuals for future Lung cancer CT screening programmes (ii) management of CT detected ‘indeterminate’ nodules (Figure 1). Figure1. Potential for the integration of biomarkers into Lung cancer CT screening programmes Figure 1 The choice of potential risk biomarkers has been recently reviewed by Atwater & Massion (1), however, the major issue is that none of the candidate biomarkers have been shown to have any impact on the reduction of cancer mortality. The question is whether we have been undertaking the correct design to identify such a molecular biomarker, which will need to add significant worth to the current risk models based on lifestyle and medical history or to the developing image-based “radiomic” biomarkers. Many diagnostic biomarkers have been described, but often these have not been designed to work alongside Lung cancer CT screening. Lung cancer risk prediction models based on epidemiological parameters and history of lung disease have made a major contribution to how we select participants for lung cancer screening trials, the two risk modes which have been used in recent lung cancer screening trials are the LLPv2 (2) (UKLS) and the PLCO2012 (3) used in the Pan Canadian trial. However, no biomarkers or genetic susceptibility markers have made any impact on these risk prediction models to date(4). The recent new set of SNPs identified in the Lung cancer OncoArray publication (5) may provide a new research avenue. Also utilising the Cancer Genome Atlas (TCGA) project dataset, 8 SNPs were found to be significantly associated with lung cancer risk ( P 0.05) in both discovery and validation phases (6). Some biomarker modalities, e.g. breath testing and liquid biopsies for microRNA (miRNA) or circulating tumour DNA (ctDNA) could impact either on risk models for selection or for managing nodules. The advent of Breath tests for early lung cancer detection has come of age and has demonstrated potential by Owlstone Medical who are in discussion with the NHS to roll out the device across GP surgeries in the UK in 2017, based on the results of the PAN Cancer Clinical trial. []. It will be important to assess how best to integrate such GP-based tests with wider screening programmes. Early lung cancer breath tests recently reviewed (7) (8). A major effort is currently been undertaken in ctDNA, the presence of cell free DNA in either plasma or serum has been described in multiple publications, however the presence of ctDNA in early disease remains elusive (9) and ctDNA is more likely to be employed in nodule management. However, circulating protein biomarkers have a more established history in lung cancer diagnosis (10) (11). The management of CT scan detected indeterminate nodules presents a major issue to the clinicians managing these patients, a number of nodule risk models have been developed, based on the characteristics of the nodules with specific epidemiological criteria (12) and pulmonary management guideline have been drawn up (13). A range of other models have been recently reviewed (14). This is now considered the forefront area of molecular biomarker research, could potentially make an enormous contribution to the management of indeterminate nodules. Liquid biopsies for microRNA (miRNA) have diagnostic and prognostic potential for CT screen detected cancers (15) (16) and may impact of nodule management (17). Pomising new research into the evaluation of tumor-derived exosomal miRNA using next-generation sequencing as a diagnostic maker for early disease has also been developed (18) (19). Circulating miRNA may also be used to improve risk models including clinical factors, imaging and serum protein levels (20). One challenge for validation and evaluation of the required molecular and imaging biomarkers is the availability of low dose CT scan data and related samples, especially in countries that have not yet instigated national screening programmes. This may be met in part by current initiatives to establish registry studies and to make imaging data available as currently been planned in the IASLC CCTRR project, but a parallel effort for access to associated minimally invasive samples (e.g. plasma and serum) would be welcomed. References 1. T. Atwater, P. P. Massion, Ann Transl Med 4, 158 (2016). 2. J. K. Field et al., Health Technol Assess 20, 1-146 (2016). 3. C. M. Tammemagi et al., J Natl Cancer Inst 103, 1058-1068 (2011). 4. M. W. Marcus et al., Int J Oncol 49, 361-370 (2016). 5. J. D. McKay et al., Nat Genet 49, 1126-1132 (2017). 6. Y. Zhang et al., Ann Oncol, (2017). 7. S. A. Hayes et al., J Breath Res 10, 034001 (2016). 8. I. Taivans et al. Expert Rev Anticancer Ther 14, 121-123 (2014). 9. C. Perez-Ramirez et al., Liquid biopsy in early stage lung cancer. Transl Lung Cancer Res 5, 517-524 (2016). 10. C. E. Hirales Casillas et al., Future Oncol 10, 1501-1513 (2014). 11. X. Wang et al., Oncotarget 8, 45345-45355 (2017). 12. A. McWilliams et al., CT. N Engl J Med 369, 910-919 (2013). 13. G. British Thoracic Society Pulmonary Nodule Guideline Development. (2016), vol. 2017. 14. J. K. Field et al. Transl Lung Cancer Res 6, 35-41 (2017). 15. M. Boeri et al.,. Proc Natl Acad Sci U S A 108, 3713-3718 (2011). 16. S. Sestini et al., Oncotarget 6, 32868-32877 (2015). 17. J. Shen et al., BMC Cancer 11, 374 (2011). 18. X. Jin et al., Clin Cancer Res, (2017). 19. Y. Lin et al., Int J Cancer, (2017). 20. Li et al. World J Surg Oncol 15, 107 (2017).

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