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Correspondence
Monitoring EGFR TKI resistance in real time using ddPCR-based liquid biopsy: a case report
  1. Laure Sorber1,2,
  2. Karen Zwaenepoel1,2,
  3. An Wouters1,
  4. Annelies Janssens3,
  5. Birgitta Hiddinga3,
  6. Jan Van Meerbeeck1,3,
  7. Filip Lardon1,
  8. Patrick Pauwels1,2,4,
  9. Christian Rolfo5
  1. 1 Center for Oncological Research Antwerp (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
  2. 2 Department of Pathology, Antwerp University Hospital (UZA), Edegem, Belgium
  3. 3 Thoracic Oncology/MOCA, Antwerp University Hospital (UZA), Edegem, Belgium
  4. 4 Biobank@UZA, Antwerp University Hospital (UZA), Edegem, Belgium
  5. 5 Phase I - Early Clinical Trials Unit - Oncology Department, Antwerp University Hospital (UZA), Edegem, Belgium
  1. Correspondence to Laure Sorber, Center for Oncological Research Antwerp (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium; Laure.Sorber{at}uantwerpen.be

http://dx.doi.org/10.1136/jclinpath-2018-205210

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    Introduction 

    Liquid biopsies, consisting of the analysis of circulating cell-free (tumour) DNA (cfDNA/ctDNA), circulating tumour cells (CTCs) or tumour-derived exosomes, have shown great potential in providing personalised therapy. Presently, the analysis of ctDNA has enabled the detection and real-time follow-up of specific genetic alterations in patients with non-small cell lung cancer (NSCLC), for which targeted therapies are available. Epidermal growth factor receptor (EGFR) activating mutations are one of the most widely known examples of targets of tyrosine kinase inhibitors (TKIs). Several studies have described the detection of the EGFR T790M resistance mutation in blood samples 15–344 days prior to disease progression based on the RECIST (Response Evaluation Criteria In Solid Tumors) criteria.1 Importantly, similar response rates to TKI therapy have been described whether the EGFR mutations were detected in blood or tissue samples.2 These findings highlight the potential of liquid biopsy as a less invasive alternative to provide personalised therapy. However, relatively few studies report the detection of other resistance mechanisms in follow-up blood samples. In this case report, we highlight a case in which digital droplet PCR (ddPCR)-based liquid biopsy aids in the detection of an atypical disease progression.

    Case report

    We present the case of a 46-year-old woman diagnosed with stage IV (extracranial metastases) EGFR-mutated lung adenocarcinoma in June 2013. Tissue samples were taken throughout the disease course as part of clinical care. The patient provided written informed consent that blood samples could be taken at several time points (figure 1). The human biological materials used in this publication were provided by Biobank@UZA (Antwerp, Belgium; ID: BE71030031000; Belgian Virtual Tumourbank funded by the National Cancer Plan; BBMRI-ERIC; no. access: …

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    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors LS designed and performed the experiments, analysed the data and wrote the manuscript. KZ assisted with the experiments. AJ, BH, JVM and CR provided patient details. KZ, AW, FL, PP and CR supervised the research and designed the experiments. All authors contributed to the final version of the manuscript with their critical revision of the manuscript.

    • Funding The authors received research grants from Pfizer, AstraZeneca, Boehringer-Ingelheim and Roche. This work was supported by the Belgian Foundation Against Cancer (grant number: FA/2014/237). AW is funded by ’Kom op tegen Kanker' (Stand up to Cancer), the Flemish Cancer Society, as postdoctoral fellow.

    • Competing interests None declared.

    • Patient consent Not required.

    • Ethics approval Ethics Committee of the Antwerp University Hospital.

    • Provenance and peer review Not commissioned; externally peer reviewed.