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Circulating Tumor DNA as a Marker for Treatment Response in Metastatic Melanoma Patients Using Next-Generation Sequencing—A Prospective Feasibility Study

Marina Berger, Andrea Thueringer, Doritt Franz, Nadia Dandachi, Emina Talakić, Georg Richtig, Erika Richtig, Peter Michael Rohrer, Lukas Koch, Ingrid Hildegard Wolf, Catharina Koch, Barbara Margaretha Rainer (+5 others)
2021 Cancers  

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We prospectively performed a longitudinal analysis of circulating tumor DNA (ctDNA) from 149 plasma samples and CT scans in Stage III and IV metastatic melanoma patients (n = 20) treated with targeted agents or immunotherapy using two custom next-generation sequencing (NGS) Ion AmpliSeq™ HD panels including 60 and 81 amplicons in 18 genes, respectively. Concordance of matching cancer-associated mutations in tissue and plasma was 73.3%. Mutant allele frequency (MAF) levels showed a range from
more » ... 4% to 28.7%, well detectable with NGS technologies utilizing single molecule tagging like the AmpliSeq™ HD workflow. Median followup time of the tissue and/or plasma positive cohort (n = 15) was 24.6 months and median progression-free survival (PFS) was 7.8 months. Higher MAF ≥ 1% at baseline was not significantly associated with a risk of progression (Odds Ratio = 0.15; p = 0.155). Although a trend could be seen, MAF levels did not differ significantly over time between patients with and without a PFS event (p = 0.745). Depending on the cell-free DNA amount, NGS achieved a sensitivity down to 0.1% MAF and allowed for parallel analysis of multiple mutations and previously unknown mutations. Our study indicates that NGS gene panels could be useful for monitoring disease burden during therapy with ctDNA in melanoma patients.
doi:10.3390/cancers13123101 pmid:34205831 pmcid:PMC8233754 fatcat:nguynhf4o5h6dcmskhplqfminu
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Marina Berger, Andrea Thueringer, Doritt Franz, Nadia Dandachi, Emina Talakić, Georg Richtig, Erika Richtig, Peter Michael Rohrer, Lukas Koch, Ingrid Hildegard Wolf, Catharina Koch, Barbara Margaretha Rainer, Maximilian Koeller, Martin Pichler, Hanno Gerritsmann, Karl Kashofer, Ariane Aigelsreiter. "Circulating Tumor DNA as a Marker for Treatment Response in Metastatic Melanoma Patients Using Next-Generation Sequencing—A Prospective Feasibility Study." Cancers 13.12 (2021) 3101