Circulating tumor DNA monitoring in peptide receptor radionuclide therapy–treated patients with gastroenteropancreatic neuroendocrine tumors.

e16321 Background: Circulating biomarkers such as chromogranin A (CgA) are commonly used in the management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but their clinical utility is limited by poor sensitivity, lack of specificity, and susceptibility to confounding factors including proton pump inhibitors, renal dysfunction, and systemic inflammation. As a tumor-agnostic marker, CgA cannot reliably track real-time disease dynamics. In contrast, circulating tumor DNA (ctDNA) offers a tumor-informed, minimally invasive strategy for monitoring treatment response and disease progression. This rertrospective series investigates ctDNA-guided disease monitoring in patients with advanced GEP-NETs treated with peptide receptor radionuclide therapy (PRRT). Methods: Four patients with metastatic, somatostatin-analogue–refractory GEP-NETs receiving PRRT were longitudinally monitored using serial ctDNA and CgA measurements alongside MRI or ⁶⁸Ga-DOTATATE PET/CT. ctDNA was assessed via a clinically validated personalized assay, Signatera, which tracks up to 16 tumor-specific variants identified by whole-exome sequencing. Results: ctDNA dynamics corresponded closely with therapeutic response and disease burden, and in some instances, changes in ctDNA levels preceded radiographic progression or stabilization. In contrast, CgA showed variable trends with limited concordance to clinical outcomes. Conclusions: Tumor-informed ctDNA can provide a sensitive, specific, and real-time molecular tool for response assessment in PRRT-treated GEP-NETs. These findings support its potential as a complementary biomarker to imaging and traditional serologic markers.