Abstract
BackgroundThe 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.MethodsForty 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.ResultsMutations 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).ConclusionctDNA 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.
Highlights
The potentials of circulating tumour DNA for non-invasive disease monitoring have been intensively studied during the last decade
A twofold circulating tumour DNA (ctDNA) concentration increase confirmed in a second successive sample predicted non-response on the following imaging in 83% of patients (10/12)
We demonstrated that quantitative ctDNA monitoring by targeted next-generation sequencing (NGS) and droplet digital PCR (ddPCR) could be used for early detection of non-response in patients with unknown genetic constitution of their tumour
Summary
The potentials of circulating tumour DNA (ctDNA) for non-invasive disease monitoring have been intensively studied during the last decade. The primary investigated ctDNA source is plasma, and the small double-stranded DNA fragments are shed both actively and passively from tumour cells to the blood stream [1,2,3]. Mutation-specific ctDNA analyses have been investigated for, among others, earlier detection of cancer disease, relapse after surgery and detection of treatment resistance mechanisms [5,6,7,8]. The potentials of circulating tumour DNA (ctDNA) have been studied for non-invasive disease monitoring in patients with targetable mutations. Our aim was to evaluate the workflow for ctDNA monitoring in a cohort of non-small cell lung cancer patients
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