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    Circulating cell free DNA during definitive chemo-radiotherapy in non-small cell lung cancer patients-Initial observations

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    Author
    Ahlborn, L.B.
    Bentzen, S.M.
    Nygård, L.
    Date
    2020
    Journal
    PLoS ONE
    Publisher
    Public Library of Science
    Type
    Article
    
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    https://doi.org/10.1371/journal.pone.0231884
    Abstract
    Background The overall aim was to investigate the change over time in circulating cell free DNA (cfDNA) in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing concurrent chemo-radiotherapy. Furthermore, to assess the possibility of detecting circulating cell free tumor DNA (ctDNA) using shallow whole genome sequencing (sWGS) and size selection. Methods Ten patients were included in a two-phase study. The first four patients had blood samples taken prior to a radiation therapy (RT) dose fraction and at 30 minutes, 1 hour and 2 hours after RT to estimate the short-term dynamics of cfDNA concentration after irradiation. The remaining six patients had one blood sample taken on six treatment days 30 minutes post treatment to measure cfDNA levels. Presence of ctDNA as indicated by chromosomal aberrations was investigated using sWGS. The sensitivity of this method was further enhanced using in silico size selection. Results cfDNA concentration from baseline to 120 min after therapy was stable within 95% tolerance limits of +/- 2 ng/ml cfDNA. Changes in cfDNA were observed during therapy with an apparent qualitative difference between adenocarcinoma (average increase of 0.69 ng/ml) and squamous cell carcinoma (average increase of 4.0 ng/ml). Tumor shrinkage on daily cone beam computer tomography scans during radiotherapy did not correlate with changes in concentration of cfDNA. Conclusion Concentrations of cfDNA remain stable during the first 2 hours after an RT fraction. However, based on the sWGS profiles, ctDNA represented only a minor fraction of cfDNA in this group of patients. The detection sensitivity of genomic alterations in ctDNA strongly increases by applying size selection. Copyright 2020 The Authors.
    Sponsors
    This work was supported by the Danish Cancer Society grant no. R72-A4605-13-S2 and National Institutes of Health (NIH) grant no. P30 CA 134274-04.
    Keyword
    circulating cell free DNA
    Carcinoma, Non-Small-Cell Lung
    Chemoradiotherapy
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083917981&doi=10.1371%2fjournal.pone.0231884&partnerID=40&md5=5bbbdf11977a404840c775c9f7594d75; http://hdl.handle.net/10713/12714
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0231884
    Scopus Count
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    UMB Open Access Articles 2020

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