Circulating Tumor DNA Monitoring in Peptide Receptor Radionuclide Therapy–Treated Patients With Gastroenteropancreatic Neuroendocrine Tumors

Peptide receptor radionuclide therapy (PRRT) represents a targeted treatment strategy for GEP-NETs, using radiolabeled somatostatin analogs to deliver therapeutic radiation to somatostain receptor 2 (SSTR2)-expressing tumor cells. 15Although functional imaging with 68 Ga-DOTATATE PET/CT (positron emission tomography/computed tomography) remains the standard for response assessment, radiographic changes may take months to manifest, delaying clinical decision making. 15Currently, there are no reliable blood-based biomarkers validated for real-time assessment of PRRT efficacy.In this retrospective case series, we evaluated four patients with metastatic, somatostatin analogue-refractory GEP-NETs treated with PRRT, whose responses were concurrently monitored using ctDNA assays and CgA levels. MethodsThis is a retrospective case review of four patients with metastatic GEP-NETs at two academic institutions in the United States.All patients underwent 177 Lu-based treatment, with concurrent longitudinal assessments of CgA and ctDNA.ctDNA was measured using Signatera (Natera Inc).Results are reported as mean tumor molecules per milliliter of plasma.Imaging modalities included 68 Ga-DOTATATE PET/CT, CT, and/or magnetic resonance imaging (MRI), as clinically indicated.Patients were identified from institutional clinics based on the following inclusion criteria: (1) diagnosis of metastatic GEP-NET; (2) treatment with 177 Lu-based PRRT; (3) ctDNA ordered at 2 time points; and (4) availability of imaging and CgA for clinical correlation.ctDNA testing was used off-label at the discretion of treating physicians.