Tumour-informed liquid biopsies to monitor advanced melanoma patients under immune checkpoint inhibition

Autor: Christopher Schroeder, Sergios Gatidis, Olga Kelemen, Leon Schütz, Irina Bonzheim, Francesc Muyas, Peter Martus, Jakob Admard, Sorin Armeanu-Ebinger, Brigitte Gückel, Thomas Küstner, Claus Garbe, Lukas Flatz, Christina Pfannenberg, Stephan Ossowski, Andrea Forschner
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-9 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-52923-0
Popis: Abstract Immune checkpoint inhibitors (ICI) have significantly improved overall survival in melanoma patients. However, 60% experience severe adverse events and early response markers are lacking. Circulating tumour DNA (ctDNA) is a promising biomarker for treatment-response and recurrence detection. The prospective PET/LIT study included 104 patients with palliative combined or adjuvant ICI. Tumour-informed sequencing panels to monitor 30 patient-specific variants were designed and 321 liquid biopsies of 87 patients sequenced. Mean sequencing depth after deduplication using UMIs was 6000x and the error rate of UMI-corrected reads was 2.47×10−4. Variant allele fractions correlated with PET/CT MTV (rho=0.69), S100 (rho=0.72), and LDH (rho=0.54). A decrease of allele fractions between T1 and T2 was associated with improved PFS and OS in the palliative cohort (p = 0.008 and p
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