Genomic Profiling of Circulating Tumor DNA Predicts Outcome and Demonstrates Tumor Evolution in ALK-Positive Non-Small Cell Lung Cancer Patients

Anne Tranberg Madsen, Anne Winther-Larsen, Tine McCulloch, Peter Meldgaard, Boe Sandahl Sorensen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

19 Citationer (Scopus)
38 Downloads (Pure)

Abstract

With the rapid development of targeted therapies for the treatment of cancer, methods for predicting response and outcome are in high demand. Non-small cell lung cancer driven by genomic rearrangements of the anaplastic lymphoma kinase (ALK) gene can be successfully treated with ALK-targeted therapy. Unfortunately, a subset of patients does not respond, and all patients ultimately acquire resistance, highlighting the need for better clinical tools to manage these patients. Here, we performed targeted next-generation sequencing on plasma circulating tumor DNA (ctDNA) from 24 patients to assess the clinical utility of ctDNA genomic profiling. Patients with detectable ctDNA prior to treatment had worse progression-free survival (PFS) than those without (median 8.7 vs. 15.2 months, p = 0.028). In addition, the presence of ctDNA within two months after treatment initiation predicted inferior PFS (median 4.6 vs. 14.5 months, p = 0.028). Longitudinal monitoring of ctDNA with droplet digital PCR during treatment reflected the radiological response and revealed potential acquired resistance mutations. Interestingly, an increase in the ctDNA concentration was evident prior to the determination of progressive disease by conventional radiological imaging, with a median lead time of 69 days (range 30–113). Genomic profiling of ctDNA is a promising tool for predicting outcome and monitoring response to targeted therapy.

OriginalsprogEngelsk
Artikelnummer947
TidsskriftCancers
Vol/bind12
Udgave nummer4
Sider (fra-til)1-13
Antal sider13
ISSN2072-6694
DOI
StatusUdgivet - 2020

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