5-Hydroxymethylcytosine profiling of plasma-derived circulating free DNA in patients with pancreatic neuroendocrine tumors treated with [177Lu]Lu-DOTA-TATE

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Introduction: Cell-free DNA (cfDNA) 5-hydroxymethylcystosine (5hmC) analysis, a novel epigenomic technology, can detect changes in tumor gene expression and regulation in liquid biopsies.

Aim(s): Utilize cfDNA 5hmC profiling to identify biomarkers associated with response and assess molecular changes in patients (pts) with pancreatic neuroendocrine tumors (pNET) treated with [177Lu]Lu-DOTA-TATE (hereafter 177Lu-DOTATATE).

Materials and methods: cfDNA 5hmC was profiled in plasma at baseline and before cycle 2. Association between baseline 5hmC profiles, 5hmC status of somatostatin receptor 2 (SSTR2) and treatment response was assessed. Gene set enrichment analysis (GSEA) identified biological pathways modulated differentially between time points, and in responders (PFS >18 months [m], median 31m) vs short-responders (PFS <14m, median 10.8m).

Conference:

Presenting Author:

Authors: Sponheim J, Wong C, Thiis-Evensen E, Coruh C, Ning Y,

Keywords: [177Lu]Lu-DOTA-TATE, Lutathera, Peptide Receptor Radionuclide Therapy, Radioligand Therapy, Pancreatic Neuroendocrine Tumor, Biobank, 5-Hydroxymethylation,