A method for treatment monitoring using circulating tumour DNA in cancer patients without targetable mutations
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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
Anne Winther-Larsen, email: Anne.Winther.Larsen@aarhus.rm.dk
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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