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Case Reports
. 2016 Aug 8:5:24.
doi: 10.1186/s40164-016-0052-3. eCollection 2015.

Non-invasive urine testing of EGFR activating mutation and T790M resistance mutation in non-small cell lung cancer

David Berz  1 , Victoria M Raymond  2 , Jordan H Garst  2 , Mark G Erlander  2
Affiliations
Case Reports

Non-invasive urine testing of EGFR activating mutation and T790M resistance mutation in non-small cell lung cancer

David Berz et al. Exp Hematol Oncol. .

Abstract

Background: The increasing understanding of non-small cell lung cancer (NSCLC) biology over the last two decades has led to the identification of multiple molecular targets. This led to the development of multiple targeted therapies in the primary and secondary resistance setting and the epidermal growth factor receptor (EGFR) gene remains the most frequently observed molecular target in NSCLC. Tissue biopsies remain the standard for the identification of such EGFR mutations. Obtaining serial tissue biopsies, especially in the secondary resistance setting is associated with multiple medical and logistical challenges. Utilizing circulating tumor DNA (ctDNA) fragments for molecular analysis can overcome these challenges and aid in therapeutic decision-making.

Case presentation: Here we present a present a 72-year-old Korean woman with metastatic, EGFR L858R mutated bronchogenic adenocarcinoma. She developed skeletal progression on treatment with first and second generation tyrosine kinase inhibitors (TKIs). Repeated biopsies failed to provide informative molecular test results. A novel urine ctDNA assay was utilized and confirmed T790M positive status. The patient was started on a third generation TKI, which led to a measurable clinical response.

Conclusions: Utilization of urine liquid biopsies for EGFR diagnostics are feasible and provided critical clinical information in this patient's case. Urine liquid biopsy represents a viable alternative to tissue biopsy, particularly in the secondary resistance setting, when tissue is not available for molecular testing.

Keywords: Cell free DNA; Circulating tumor DNA; Diagnostics; EGFR; Liquid biopsy; Lung cancer; Targeted therapy; Urine; ctDNA.

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Figures

Fig. 1
Fig. 1
a Diagnostic imaging from September 2013, 2 cm left lower lobe lesion, multilevel mediastinal involvement, and numerous hypermetabolic skeletal lesions. b May 2014 PET-CT demonstrating new hypermetabolic lesion at T12. c January 2015 attempted CT guided biopsy of T12 lesion. d August 2015 PET-CT demonstrating response to third generation TKI following identification of EGFR resistance mutation
Fig. 2
Fig. 2
Urine ctDNA test results confirming presence of EGFR L858R activating mutation and emergence of EGFR T790M resistance mutation
Fig. 3
Fig. 3
Timeline of therapy, diagnostic evaluation, and patient status
See this image and copyright information in PMC

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