Research Papers:

A method for treatment monitoring using circulating tumour DNA in cancer patients without targetable mutations

Christina Demuth, Anne Winther-Larsen _, Anne Tranberg Madsen, Peter Meldgaard and Boe Sandahl Sorensen

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Oncotarget. 2018; 9:31066-31076. https://doi.org/10.18632/oncotarget.25779

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Christina Demuth1,*, Anne Winther-Larsen1,*, Anne Tranberg Madsen1, Peter Meldgaard2 and Boe Sandahl Sorensen1

1Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

2Department of Oncology, Aarhus University Hospital, Aarhus, Denmark

*These authors have contributed equally to this work

Correspondence to:

Anne Winther-Larsen, email: [email protected]

Keywords: circulating tumour DNA; non-small cell lung cancer; next-generation sequencing; digital PCR; wild-type EGFR

Received: February 12, 2018     Accepted: June 12, 2018     Published: July 24, 2018


Background: The potentials of circulating tumour DNA (ctDNA) have been studied for non-invasive disease monitoring in patients with targetable mutations. However, the majority of cancer patients harbour no targetable mutations. A workflow including targeted next-generation sequencing (NGS) and droplet digital PCR (ddPCR) could be used for monitoring treatment in these patients. Thus, our aim was to evaluate the workflow for ctDNA monitoring in a cohort of non-small cell lung cancer patients.

Methods: Forty patients were prospectively included. Plasma samples were collected prior to and during treatment. NGS (Ion AmpliSeq Colon and Lung Cancer panel v2) was performed on ctDNA from pre-treatment samples. The identified mutations were monitored by ddPCR in consecutively collected samples.

Results: Mutations were detected in 21 patients. The most commonly mutated genes were TP53 (N=20) and KRAS (N=13). Treatment was discontinued due to non-response in 18 patients. In 16 of these, a simultaneous increase in ctDNA concentration was observed. A twofold ctDNA concentration increase confirmed in a second successive sample predicted non-response on the following imaging in 83% of patients (10/12).

Conclusion: ctDNA monitoring can be used for early detection of non-response in patients without targetable mutations, and therefore could supplement imaging data for treatment monitoring in this subset of patients.

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